Information Sheets - ��ݮ��Ƶ

AMS Guide to MHT/HRT Doses Australia only

2025-03-11T00:00:00+11:00

This Information Sheet has been developed as a guideline only to MHT/HRT products available in Australia in November 2024. Hormone Replacement Therapy (HRT) is now referred to as Menopausal Hormone Therapy (MHT). The intention of this sheet is to help clinicians change their patients to higher or lower approximate doses of MHT if needing to tailor therapy, or remain within the same approximate dose if needing to change brands of MHT. Private/non-PBS script products are marked with an *

AMS Guide to MHT/HRT Doses Australia124.93 KB

CYCLIC MENOPAUSAL HORMONE THERAPY (MHT)

Use continuous oestrogen and cyclic progestogen combinations at perimenopause or if less than 12 months amenorrhoea

LOW DOSE
PRODUCT	PRESENTATION	COMPOSITION
Femoston	Tablet	1mg oestradiol/10mg dydrogesterone
Estrogel Pro	Combination pack of oestradiol transdermal gel, with micronised progesterone capsules.	1 pump (0.75mg oestradiol) daily, and 2 capsules (200mg) micronised progesterone orally for 12 days out of a 28-day cycle
Medium dose
Trisequens*	Tablet	1 and 2mg oestradiol hemihydrate/1mg norethisterone acetate
Femoston	Tablet	2mg oestradiol/10mg dydrogesterone
Estalis sequi 50/140)	Transdermal patch	50mcg 17β oestradiol/140mcg norethisterone acetate (twice weekly application)
Estalis sequi 50/250 (same oestrogen, more progestogen than Estalis sequi 50/140)	Transdermal patch	50mcg 17β oestradiol/250mcg norethisterone acetate (twice weekly application)
Estrogel Pro	Combination pack of oestradiol transdermal gel, with micronised progesterone capsules.	2 pumps (1.5mg oestradiol) daily, and 2 capsules (200mg) micronised progesterone orally for 12 days out of a 28-day cycle

CONTINUOUS COMBINED MENOPAUSAL HORMONE THERAPY (MHT)

Should be used if 12 months since LMP or after 12 months cyclical MHT

LOW DOSE
PRODUCT	PRESENTATION	COMPOSITION
Angeliq1/2*	Tablet	1mg oestradiol hemihydrate/2mg drospirenone
Femoston-conti*	Tablet	1mg oestradiol/5mg dydrogesterone
Kliovance*	Tablet	1mg oestradiol hemihydrate/0.5mg norethistrone
Bijuva*	Capsule	1mg oestradiol/100mg micronised progesterone
Estrogel Pro	Combination pack of oestradiol transdermal gel, with micronised progesterone capsules.	1 pump (0.75mg oestradiol hemihydrate) daily, and 1 capsule (100mg) micronised progesterone orally for 25 days out of a 28-day cycle
OTHER LOW DOSE HORMONAL OPTIONS
Livial, Xyvion	tablet	2.5mg tibolone
Duavive* (oestrogen/ SERM combination)	tablet	0.45mg conjugated equine oestrogens / 20mg bazedoxifene acetate
MEDIUM DOSE
Kliogest*	Tablet	2mg oestradiol hemihydrate/1mg norethistrone
Estalis continuous 50/140	Transdermal patch	50mcg 17β oestradiol/140mcg norethisterone acetate (twice weekly application)
Estalis continuous 50/250 (same oestrogen, more progestogen than Estalis continuous 50/140)	Transdermal patch	50mcg 17β oestradiol/250mcg norethisterone acetate (twice weekly application)
Estrogel Pro	Combination pack of oestradiol transdermal gel, with micronised progesterone capsules.	2 pumps (1.5mg oestradiol hemihydrate) daily, and 1 capsule (100mg) micronised progesterone orally for 25 days out of a 28-day cycle¹

¹Can be given daily if adherence is an issue

OESTROGEN ONLY THERAPY:

Only use these if patient has had a hysterectomy or in combination with a progestogen or Mirena if intact uterus

LOW DOSE
PRODUCT	PRESENTATION	COMPOSITION
Estrofem*	Tablet	1mg oestradiol hemihydrate
Progynova	Tablet	1mg oestradiol valerate
Premarin*	Tablet	0.3mg conjugated equine oestrogens
Estradot 25, 37.5	Transdermal patch	25mcg or 37.5 mcg oestradiol (twice weekly application)
Estraderm 25 MX	Transdermal patch	25mcg oestradiol hemihydrate (twice weekly application)
Estrogel	Gel	0.75mg oestradiol hemihydrate= 1 pump daily
Sandrena	Gel	0.5mg oestradiol daily
MEDIUM DOSE
*Estrofem, Zumenon**	Tablet	2mg oestradiol hemihydrate
Progynova	Tablet	2mg oestradiol
Premarin*	Tablet	0.625mg conjugated equine oestrogens
Estradot 50	Transdermal patch	50mcg oestradiol (twice weekly application)
Estraderm 50 MX	Transdermal patch	50mcg oestradiol hemihydrate (twice weekly application)
Sandrena	Gel	1mg oestradiol daily
Estrogel	Gel	1.5mg oestradiol hemihydrate = 2 pumps daily
HIGH DOSE
Estradot 75, 100	Transdermal patch	75 or 100mcg oestradiol (twice weekly application)
Estraderm 75, 100 MX	Transdermal patch	75 or 100mcg oestradiol hemihydrate (twice weekly application)
Estradot 100, Estraderm 100 MX	Transdermal patch	100mcg oestradiol hemihydrate (twice weekly application)
Sandrena	Gel	1.5mg = 1mg + 0.5mg sachets daily
Estrogel	Gel	2.25mg oestradiol hemihydrate = 3 pumps daily or 3.0mg oestradiol = 4 pumps daily
VAGINAL THERAPY
If prescribing vaginal oestrogen rather than systemic hormone therapy, a progestogen is not required.
PRODUCT	PRESENTATION	COMPOSITION
Ovestin Ovestin	Cream Pessary	0.5mg oestriol = 1 application; daily for first 14 days, then twice weekly ongoing 0.5mg oestriol; daily for first 14 days, then twice weekly ongoing
Vagifem Low	Pessary	10mcg oestradiol hemihydrate; daily for first 14 days, then twice weekly ongoing
Intrarosa	Pessary	6.5mg dehydroepiandrosterone (DHEA) daily (prasterone)

PROGESTOGEN THERAPY

Suggested alternative doses for use with the oestrogen preparations above where fixed dose therapy is not suitable

LOW DOSE FOR USE WITH LOW DOSE OESTROGEN
PRODUCT	PRESENTATION	COMPOSITION
Provera (1/2 of 5mg tablet)	Tablet	2.5mg medroxyprogesterone acetate
Provera 2.5mg tablet*	Tablet	2.5mg medroxyprogesterone acetate
Primolut N (1/4 of 5mg tablet)	Tablet	1.25 mg norethisterone
Prometrium	Capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹ or 200mg orally daily for 12 days out of a 28-day cycle
*Mirena(**PBS indication for contraception/menorrhagia)	Intrauterine system	Levonorgestrel 52mg (approx. 20mcg daily over 5 years)
MEDIUM DOSE FOR USE WITH MEDIUM DOSE OESTROGEN ²
PRODUCT	PRESENTATION	DOSE
Primolut N (1/4 of 5mg tablet)	Tablet	1.25 mg norethisterone
Provera, Ralovera	Tablet	5mg medroxyprogesterone acetate
Prometrium	Capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹ or 200mg orally for 12 days out of a 28-day cycle
Mirena* (PBS indication for contraception/menorrhagia)	Intrauterine system	Levonorgestrel 52mg (approx. 20mcg daily over 5 years)
HIGHER DOSE (FOR USE IN CYCLICAL THERAPY OR CONTINUOUS THERAPY WITH HIGH DOSE OESTROGEN)²
Primolut N (1/2 5mg tablet)	Tablet	2.5mg norethisterone
Prometrium	capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹ or 200mg orally for 12 days out of a 28-day cycle
Provera, Ralovera	Tablet	10mg medroxyprogesterone acetate
Mirena* (PBS indication for contraception/menorrhagia)	Intrauterine system	Levonorgestrel 52mg (approx. 20mcg daily over 5 years)

Notes

¹Can be given daily if adherence is an issue

²There are insufficient data for the need to increase the dose of micronised progesterone with higher oestrogen doses, or safety of higher doses. Therefore, the current recommendation is 200mg of progesterone for 12 days on a cyclical regimen or 100mg per day on a continuous regimen. This may not be enough in terms of unscheduled bleeding with higher doses of oestrogen.

Patients commenced on continuous combined MHT should not bleed after the first 6 months of use. If they do bleed, they need investigating. Those using combined cyclic therapy should have a withdrawal bleed around the end of the progestogen phase and if they bleed out of cycle, too long or too heavily, they also need investigating.

If investigation of unscheduled or out of cycle bleeding discloses no endometrial abnormality, it may be appropriate to increase the dose of progestogen to 200mg daily for women using high dose oestrogen on a continuous regimen and to 300-400mg for 12 days per month for those using high dose oestrogen on a cyclic regimen.

The use of oestrogen plus progestogen is intended to reduce the risk of endometrial cancer to the level seen in an untreated population and not to zero. Consequently, women and their doctors should be aware of the importance of investigating any postmenopausal bleeding (see AMS Information Sheet Bleeding – perimenopausal, postmenopausal and breakthrough bleeding on MHT/HRT).

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NOTE: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person’s circumstances and should always be discussed with that person’s own healthcare provider. This Information Sheet contains copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. No other reproduction or transmission is permitted in any form or by any information storage and retrieval systems except as permitted under the Copyright Act 1968 or with prior written permission from the copyright owner. ID:2024-12-16

Content Updated 11 March 2025

AMS Guide to MHT/HRT Doses New Zealand only

2024-10-21T00:00:00+11:00

This Information Sheet has been developed as a guideline only to MHT/HRT products available in New Zealand in September 2024. Hormone Replacement Therapy (HRT) is now referred to as Menopausal Hormone Therapy (MHT). The intention of this sheet is to help clinicians change their patients to higher or lower approximate doses of MHT if needing to tailor therapy, or remain within the same approximate dose if needing to change brands of MHT. Private/non Pharmac subsidised script products are marked with an *.

AMS Guide to MHT/HRT Doses NZ107.2 KB

PROGESTOGEN

Suggested alternative doses for use with the oestrogen preparations above where fixed dose therapy is not suitable

LOW DOSE for use with low dose oestrogen
PRODUCT	PRESENTATION	COMPOSITION
Provera (½ of 5mg tablet)	Tablet	2.5mg medroxyprogesterone acetate
Provera 2.5mg tablet*	Tablet	2.5mg medroxyprogesterone acetate
Primolut N (¼ of 5mg tablet)	Tablet	1.25 mg norethisterone
Utrogestan*	Capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹ or 200mg orally daily for 12 days out of a 28-day cycle
Mirena* (Pharmac indication for menorrhagia/anaemia)	Device (5 years)	20mcg/24hrs levonorgestrel
MEDIUM DOSE for use with medium dose oestrogen²
Primolut N (¼ of 5mg tablet)	Tablet	1.25 mg norethisterone
Provera	Tablet	5mg medroxyprogesterone acetate
Utrogestan*	Capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹ or 200mg orally for 12 days out of a 28-day cycle
Mirena* (Pharmac indication for menorrhagia/anaemia)	Device (5 years)	20mcg/24hrs levonorgestrel
HIGHER DOSE (for use in cyclic therapy or continuous therapy with high dose oestrogen)²
Primolut N (1/2 5mg tablet)	Tablet	2.5mg norethisterone
Provera	Tablet	10mg medroxyprogesterone acetate
Utrogestan*	Capsule	100mg micronised progesterone orally for 25 days out of a 28-day cycle¹or 200mg orally for 12 days out of a 28-day cycle
Mirena* (Pharmac indication for menorrhagia/anaemia)	Device (5 years)	20mcg/24hrs levonorgestrel

Can be used daily if compliance is an issue.
Safe continuous or cyclic dose of micronised progesterone for use with oestradiol 2mg tablets is unknown due to insufficient data.
Safe continuous or cyclic dose of micronised progesterone for use with high dose oestrogen (75mcg patch or higher, or high dose oestrogel gels) is unknown due to insufficient data.

OESTROGEN ONLY THERAPY

Only use these if patient has had a hysterectomy or in combination with a progestogen or Mirena if intact uterus

LOW DOSE
PRODUCT	PRESENTATION	COMPOSITION
Estrofem*	Tablet	1mg oestradiol hemihydrate
Progynova	Tablet	1mg oestradiol valerate
Premarin*	Tablet	0.3mg conjugated equine oestrogen
Estradot 25^#	Transdermal patch	25 /24hrs 17Β oestradiol (twice weekly application)
Estrogel	Gel	0.75mg oestradiol hemihydrate= 1 pump
MEDIUM DOSE
Progynova	Tablet	2mg oestradiol valerate
Estradot 50	Transdermal patch	50mcg/24 hours oestradiol (twice weekly application)
Premarin*	Tablet	0.625mg conjugated equine oestrogens
*Sandrena^#**	Gel	1mg oestradiol (daily application)
Estrogel	Gel	1.5mg oestradiol hemihydrate = 2 pumps
HIGH DOSE
Estradot 75 Estradot 100	Transdermal patch	75 or 100mcg/24 hours (twice weekly application)
Estrogel	Gel	2.25mg oestradiol hemihydrate = 3 pumps or 3.0mg oestradiol hemihydrate = 4 pumps
Oestradiol implants - No longer available
OESTROGEN ONLY VAGINAL THERAPY
If prescribing vaginal oestrogen rather than systemic hormone therapy, a progestogen is not required.
Product	Presentation	Composition
Ovestin Ovestin	Cream Pessary	1mg/g oestriol 0.5mg oestriol

# Note Sandrena is only available under Section 29 at online pharmacies.

# Note there is currently a shortage of Estradot so please prescribe Oestradiol patches to allow for substitutes to be dispensed

CYCLICAL OESTROGEN AND PROGESTOGEN COMBINATION MHT

Use cyclical oestrogen and progestogen combinations at peri-menopause or if less than 12 months amenorrhoea

MEDIUM DOSE
Trisequens*	Tablet	1 and 2mg oestradiol hemihydrate/1mg norethisterone acetate

CONTINUOUS OESTROGEN AND PROGESTOGEN COMBINATIONS

Should be used if 12 months since LMP or after 12 months cyclical MHT

LOW DOSE
PRODUCT	PRESENTATION	COMPOSITION
Kliovance*	Tablet	1mg oestradiol hemihydrate/0.5mg norethistrone acetate
OTHER LOW DOSE HORMONAL OPTIONS
Livial, Xyvion	Tablet	2.5mg tibolone
Duavive* (oestrogen/SERM combination)	Tablet	0.45mg conjugated equine oestrogens / 20mg bazedoxifene acetate
MEDIUM DOSE
Kliogest*	Tablet	2mg oestradiol/1mg norethistrone acetate

Note: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person’s circumstances and should always be discussed with that person’s own healthcare provider. This Information Sheet contains copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. No other reproduction or transmission is permitted in any form or by any information storage and retrieval systems except as permitted under the Copyright Act 1968 or with prior written permission from the copyright owner. ID:2024-17-10

Content Updated December 2024

AMS Symptom Score Card

2025-02-25T00:00:00+11:00

AMS symptom score card110.92 KB

Note: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person’s circumstances and should always be discussed with that person's own healthcare provider. This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the ��ݮ��Ƶ. ID:2025-02-20 © ��ݮ��Ƶ Ltd 2025

Content updated February 2025

Bioidentical custom compounded hormone therapy

2018-05-18T11:00:00+10:00

Key Points:

Conventional MHT often contains the same form of body-identical hormones as compounded therapies.
The patient must be fully informed that custom compounded bioidentical hormone therapy is unproven and that there may be risks, particularly the lack of endometrial protection.
In the absence of peer-reviewed scientific data, and for all the other reasons mentioned below, the ��ݮ��Ƶ cannot endorse the use of compounded bioidentical hormone therapies.

AMS Bioidentical Hormones for Menopausal Symptoms334.48 KB

Many patients are attracted to the concept of using hormones that are the same as those which are produced by the ovary pre-menopause. This gained traction after the publication of the Women’s Health Initiative study. There was a suggestion from some that the adverse findings were secondary to the “synthetic” hormones used in that study and that the same would not occur with the use of natural hormones. This has led to an industry of the compounding of ‘bioidentical’ hormones which are often in the form of creams, troches and pessaries. These are widely used by many women at considerable expense.

‘Bioidentical’ hormone therapy refers to compounded products which are marketed as hormones that are identical to those produced by the body. The production of these products is not subject to the regulatory conditions of approved pharmaceutical products (1).

In contrast ‘body-identical’ hormone therapy refers to pharmaceutical products that have the same chemical structure as those produced in the human body (1).

It is important to realise that no hormone used in any preparation of pharmaceutical grade menopausal hormone therapy (MHT) or compounded “bioidentical therapy” is ‘natural’. They are all synthesised in the laboratory from some precursor by enzymatic manipulation.

Furthermore, oestrogens all act through the same receptors, although different progestogens interact with other steroid receptors as well as with the progesterone receptor.

Do compounded bio-identical hormones work?

The efficacy of oestrogen preparations for menopausal symptoms may be measured by the resolution of vasomotor symptoms. There are no data on the efficacy of compounded oestrogen therapies for the maintenance of bone density and prevention of osteoporosis.

For progestogens, the measure of efficacy is the prevention of endometrial hyperplasia and neoplasia. The progestogen regimens used are variable and unregulated, and there are no data on whether they are adequate to provide endometrial protection with evidence to suggest they are not (see below).

Safety concerns about compounded bioidentical hormones

Risk of endometrial hyperplasia and neoplasia

A major concern is the question of adequate endometrial protection with compounded progestogen regimens. Here, significant failings have been documented, in that compounded progesterone delivery, both by transdermal and troche route, have been reported to be inadequate for endometrial protection when administered in combination with oestrogen, leading to endometrial cancer (2, 3).

Quality control and contaminants

Pharmaceutical grade hormone therapies are manufactured under strict conditions and are required to undergo rigorous testing of content purity and efficacy. Custom compounded hormones are produced under unregulated conditions without quality standards regarding content, efficacy, or contamination. It is impossible to know what excipients are in the preparations and how those excipients will affect pharmacokinetics (4). Contamination of compounded therapies may contain impurities which compromise sterility or those which lead to more serious consequences (5, 6).

Content of commonly prescribed compounded therapy

Oestrogens

Oestrogen in compounded therapies is often delivered as “biest” (oestradiol and oestriol) or “triest” (oestradiol, oestrone and oestriol). Although all three forms of oestrogen are naturally present in the circulation, oestrone and oestriol function as competitive inhibitors of oestradiol at the oestrogen receptor and exogenous oestradiol will be metabolised in vivo to oestrone and oestradiol. There is no evidence to support the exogenous provision of all three forms in hormone replacement.

Progestogens

Progestins (synthetic progestogens) act at different receptors of the steroid receptor family and there is some evidence that their differential effects are as a result of this, e.g. cyproterone acetate is an anti-androgenic progestin with some glucocorticoid action and drospirenone has some anti-mineralocorticoid action. There is also some evidence that body-identical progesterone has a better risk-benefit profile, when delivered in sufficient amount, to most other members of the progestogen family (7). However, delivery of progesterone in sufficient therapeutic doses is the important issue, and neither troche nor transdermal therapy does this reliably.

Other hormones

Other hormones, such as DHEA, pregnenolone (which is a precursor for cortisol), testosterone, growth hormone, thyroxine and melatonin are commonly included in custom-compounded hormone therapy. Many of these substances are prescription medicines for specific conditions other than menopausal symptoms and have the potential for adverse events from misuse.

Salivary hormone testing

Proponents of compounded MHT often advocate salivary hormone testing in order to individualise doses and monitor adequacy of therapy. However, unlike laboratory methods for hormones in blood, laboratory methods for measuring salivary hormones are not standardised and do not have quality control programs. Reproducibility of salivary hormone methods is affected by salivary flow rates, which are in turn affected by state of hydration and food intake. Both salivary and blood hormone levels are affected by recent intake of exogenous hormone. Neither blood nor salivary hormone measures should be used to judge appropriateness of dose. The exception to this is the measurement of oestradiol in blood in users of oestradiol implants to avoid tachyphylaxis. In all other cases adequacy of oestrogen dose is judged by resolution of symptoms, and/or maintenance of bone density.

Pharmacy Board Guidelines

The Pharmacy Board of Australia has issued guidelines on the compounding of medicines. The Guidelines state that a compounded medicine should be prepared only in circumstances where: a) an appropriate commercial product is unavailable, b) a commercial product is unsuitable (e.g. if a patient experienced an allergy to an excipient in the commercial product), or c) when undertaking research sanctioned by a recognised human research ethics committee (8).

Compounded MHT is being prescribed and dispensed outside these guidelines as there are appropriate commercial products available which deliver effective therapy as guided by results from clinical trial research. Moreover, there are commercial products which deliver body-identical oestradiol and progesterone, if the prescribing doctor or the patient so wishes.

Availability of pharmaceutical grade body-identical hormones.

Pharmaceutical grade oestradiol is available in Australia and New Zealand as tablets, transdermal patches or gel. It is also available for topical vaginal treatment.

Pharmaceutical grade body-identical progesterone is now available in capsule form in Australia (as Prometrium) and NZ (as Utrogestan).

Therefore, if women and their doctors wish to use hormones that are body-identical, this can be achieved with approved regulated products. In this way women can avoid the potential dangers of compounded products, maintain appropriate monitoring of safety and efficacy, and in most cases, save money.

See Information sheets

AMS Guide to Equivalent MHT/HRT Doses Australia only

AMS Guide to Equivalent MHT/HRT Doses New Zealand only

Oestrogen Only Menopausal Hormone Therapy

Combined Menopausal Hormone Therapy (MHT)

The International Menopause Society, American College of Obstetricians and Gynecologists, The Endocrine Society, the North American Menopause Society (NAMS), United States Food and Drug Administration, American Medical Association and the American Society for Reproductive Medicine Practice Committee have all released statements advising against the use of compounded therapy until evidence is produced with regard to efficacy and safety. With such diverse content mix, production sites and methods, that is unlikely to be forthcoming.

References:

Files JA, Ko MG, Pruthi S. Bioidentical hormone therapy. Mayo Clin Proc. 2011;86(7):673-80.
Eden JA, Hacker NF, Fortune M. Three cases of endometrial cancer associated with "bioidentical" hormone replacement therapy. Med J Aust. 2007;187(4):244-5.
Davis R, Batur P, Thacker HL. Risks and effectiveness of compounded bioidentical hormone therapy: a case series. Journal of Women's Health. 2014;23(8):642-8.
Santoro N, Braunstein GD, Butts CL, Martin KA, McDermott M, Pinkerton JV. Compounded bioidentical hormones in endocrinology practice: an Endocrine Society Scientific Statement. J Clin Endocrinol Metab. 2016;101(4):1318-43.
Smith RM, Schaefer MK, Kainer MA, Wise M, Finks J, Duwve J, et al. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2013;369(17):1598-609.
Poon WT, Lam YH, Lee HHC, Ching CK, Chan WT, Chan SS, et al. Outbreak of hypoglycaemia: sexual enhancement products containing oral hypoglycaemic agent. Hong Kong Medical Journal. 2009;15(3):196-200.
Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.[Erratum appears in Breast Cancer Res Treat. 2008 Jan;107(2):307-8]. Breast Cancer Res Treat. 2008 Jan;107(1):103-11.
Pharmacy Board of Australia. Guidelines on compounding of medicines 2015 updated 2017.

Note: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person's circumstances and should always be discussed with that person's own healthcare provider. This Information Sheet contains copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. No other reproduction or transmission is permitted in any form or by any information storage and retrieval systems except as permitted under the Copyright Act 1968 or with prior written permission from the copyright owner.

Content updated May 2018

Bleeding – perimenopausal, postmenopausal and breakthrough bleeding on MHT/HRT

2024-01-25T10:36:08+11:00

Key points

A change in bleeding pattern is common during perimenopause.
Heavy bleeding, prolonged bleeding and any bleeding more than 12 months after the last menstrual period needs investigation.
Endometrial ultrasound is the initial investigation of choice and the findings determine the need for tissue sampling and/or hysteroscopy.
Medical management, after excluding a localised or neoplastic lesion, involves modification of the MHT dose or regimen.

Bleeding – perimenopausal, postmenopausal and breakthrough bleeding on MHT/HRT247.86 KB

Perimenopausal bleeding

In the menopausal transition, hormonal fluxes may be erratic with vaginal bleeding being both ovulatory or non-ovulatory, light or heavy, reasonably regular or entirely irregular (1). For women considering menopausal hormone therapy (MHT), abnormal bleeding should be investigated before prescribing. Heavy menstrual bleeding, rather than irregular bleeding itself is a hallmark of abnormal build-up of the endometrium. Heavy bleeding after a prolonged interval without bleeding, or prolonged bleeding of any amount should be investigated. A lower investigative threshold should apply for high-risk women.

Postmenopausal bleeding

Postmenopausal bleeding (PMB) refers to any vaginal bleeding that occurs in a menopausal woman ie. 12 months after their final menstrual period. This does not include the regular withdrawal bleed that occurs on MHT.

Any postmenopausal bleeding requires investigation to exclude a sinister cause. The likelihood of endometrial carcinoma for a woman presenting with PMB is 10% (2). However, around 95% of women with endometrial malignancy will present with PMB (3). Risk factors for endometrial cancer include age, obesity, use of unopposed oestrogen, polycystic ovary syndrome, Type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology and family history of gynaecologic malignancy(4). Nulliparity is also a risk factor. Patients taking non-conventional MHT, such as troches and transdermal progestogen are at risk of endometrial hyperplasia and cancer (5).

Women on menopausal hormone therapy

In women taking cyclical MHT, a withdrawal bleed is expected and the patient should be counselled as such. The withdrawal bleed should occur toward the end of, or after the progestogen containing phase of the cyclical regimen. Bleeding which is unpredictable, occurring outside the expected time, or excessively heavy should be investigated.

For women taking continuous combined MHT (CCMHT), the significance of breakthrough bleeding depends upon the recency of her LMP and on how long she has been taking CCMHT. Women within 12 months of the last natural menstrual period often do not achieve amenorrhoea, presumably because some residual endogenously oestrogen-stimulated endometrium is present. Unpredictable breakthrough bleeding is common in this situation and does not need investigation, unless it is unusually heavy. To avoid this, it is recommended that cyclical MHT be used for the first 12 months at least following the LMP. A similar diagnostic and therapeutic approach applies to tibolone.

Bleeding should be investigated if it occurs after six months use of CCMHT or tibolone, or starts after amenorrhoea has been established on this regimen. Amenorrhoea in this setting depends upon the balance between the oestrogenic effect and progestogenic effect of the MHT components on the endometrium. Oestrogen stimulation of the endometrium causes proliferative histological features and progesterone secretory. Inadequate progestogenic effect can therefore result in endometrial proliferation and possibly hyperplasia and bleeding. It may, like unopposed oestrogen therapy, lead to endometrial malignancy. However, more commonly in women taking pharmaceutical preparations of CCMHT, excessive progestogenic effect may produce bleeding from an atrophic endometrium.

Diagnostic evaluation of postmenopausal bleeding (PMB)

The primary goal of investigation is to exclude malignancy, and secondarily to elucidate a treatable non-malignant cause (6).

A detailed history should be taken:

When does the bleeding occur?
Is it post-coital?
What medications is the patient taking eg. anticoagulants, herbal therapies, tamoxifen
Is the patient taking so-called “bioidentical” hormones?
Has the patient missed MHT doses?
When was the last cervical screening test?
Are there any bladder or bowel symptoms?

Physical examination should include inspection of the vulva, vagina and the cervix for visual evidence of lesions or bleeding, taking note of any signs of atrophy. Bleeding from the perineum, urethra and anus is also a possibility. A cervical co-test (HPV test and liquid based cytology) or cervical smear should be done.

Endometrial ultrasound

Endometrial ultrasound is the initial investigation of choice. This should be done by an experienced specialist gynaecological ultrasonographer and with transvaginal ultrasound (TVUS). In women taking cyclical MHT, it should be done immediately after the withdrawal bleed (7). The ultrasound should be able to identify any localised uterine lesion which may contribute to bleeding – endometrial polyp, submucosal fibroid, hyperplasia or cancer. The significance of PMB for the risk of malignancy differs with use of MHT and endometrial thickness on TVUS. Subsequent investigations depend on the ultrasound findings, so the experience of the ultrasonographer is critical. After excluding localised lesions, the following algorithm is useful (8). Note that this algorithm does not apply to women taking tamoxifen.

Figure 1. Management algorithm for patients with post-menopausal bleeding (8). ECC= Endometrial echo complex, EC= Endometrial carcinoma, EMB= Endometrial biopsy

Tamoxifen therapy

Tamoxifen therapy is associated with stimulation of the endometrium and an increased risk of endometrial cancer (9). Tamoxifen therapy invariably produces a thickened appearance to the endometrium which is not always indicative of neoplasia. Therefore, TVUS is not useful for the investigation of PMB in a woman on tamoxifen therapy and examination of the uterine cavity by hysteroscopy is recommended (6).

Histological assessment

There has been some debate for what is regarded as the upper limit of normal endometrial thickness. Many groups have recently used a cut-off of 4mm (4,10,11). An endometrial thickness of ≤4mm has a 99% negative predictive value for malignancy (4).

Endometrial biopsy should be performed in women who meet the following criteria(4):

Endometrial thickness >4mm
Not easy display of the endometrium eg. fibroids
Persistent PMB
Suspicion of polyp or mass on transvaginal ultrasound
Endometrial thickness ≥ 3mm with fluid in the endometrial cavity

Blind tissue sampling such as Pipelle or D&C may be sufficient for pathology that affects the entire endometrial surface, but it is inadequate for detecting localised lesions such as endometrial polyps, which may be malignant (6). Hysteroscopy is superior to endometrial biopsy and ultrasonography for the identification of these structural lesions and is recommended.

Management

Medical management

When a localised or neoplastic lesion is found, the management is surgical. However, when the findings are benign and the patient is taking MHT, some modification of the MHT dose or regimen is required. While there is an abundance of literature about the incidence of bleeding on MHT and the histological findings, there are no evidence-based recommendations guiding therapeutic intervention. Therefore, the following recommendations are based on clinical practice advice from the literature and based on the patterns of histology seen in women with breakthrough bleeding (12-15). They are made here with the proviso that continued bleeding should prompt re-investigation, as above.

a) Cyclical MHT with unpredictable bleeding and negative histological screen for pathology
This may respond to a change in the progestogen component of the MHT such as altering the dose, type of progestogen or the mode of delivery eg. intrauterine.

b) CCMHT with breakthrough bleeding, endometrium >4mm and negative histology
If less than 12 months post LMP, change to cyclical MHT or intrauterine progestogen. If more than 12 months post LMP, change oestrogen/progestogen balance by reducing oestrogen or changing progestogen dose, type or delivery.

c) CCMHT with breakthrough bleeding, endometrium <4mm
This is the most difficult scenario to manage, especially in a patient who wants to have no withdrawal bleeding. The TVUS suggests adequate, if not excessive, progestogenic effect, especially if tissue sampling demonstrates an atrophic sample. Increasing the dose or changing the progestogen formulation does not always address the underlying problem. Continuous progestogen effect on the endometrium exposes superficial dilated blood vessels which predispose to bleeding (16). The same may occur with prolonged tibolone therapy. A change back to cyclical MHT, at least for a while, is recommended or an increase in the oestrogen dose may be effective.

Surgical management

Surgical management is appropriate for neoplastic and local lesions causing bleeding. However, women who have heavy or unmanageable breakthrough bleeding in the absence of pathology, may prefer to have a hysterectomy, after which they need take only oestrogen as MHT. The alternative is endometrial ablation. This may resolve the PMB but it should be noted that progestogen is still necessary since there will be residual endometrium left. Moreover, the above investigations – TVUS, hysteroscopy, endometrial sampling - will be difficult if there is subsequent PMB (17).

References

Hale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS. Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition. Menopause. 2009;16(1):50-9.
van Hanegem N, Breijer MC, Khan KS, Clark TJ, Burger MP, Mol BW, et al. Diagnostic evaluation of the endometrium in postmenopausal bleeding: an evidence-based approach. Maturitas. 2011;68(2):155-64.
van Hanegem N, Prins MM, Bongers MY, Opmeer BC, Sahota DS, Mol BW, et al. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2016;197:147-55.
ACOG Committee Opinion No. 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding. Obstet Gynecol. 2018;131(5):e124-e9.
Eden JA, Hacker NF, Fortune M. Three cases of endometrial cancer associated with "bioidentical" hormone replacement therapy. Med J Aust. 2007;187(4):244-5.
Munro MG, Southern California Permanente Medical Group's Abnormal Uterine Bleeding Working G. Investigation of women with postmenopausal uterine bleeding: clinical practice recommendations. Perm J. 2014;18(1):55-70.
Affinito P, Palomba S, Sammartino A, Bonifacio M, Nappi C. Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women. Maturitas. 2001;39(3):239-44.
Carugno J. Clinical management of vaginal bleeding in postmenopausal women. Climacteric. 2020;23(4):343-9.
Mourits MJ, De Vries EG, Willemse PH, Ten Hoor KA, Hollema H, Van der Zee AG. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol. 2001;97(5 Pt 2):855-66.
Saccardi C, Spagnol G, Bonaldo G, Marchetti M, Tozzi R, Noventa M. New Light on Endometrial Thickness as a Risk Factor of Cancer: What Do Clinicians Need to Know? Cancer Manag Res. 2022;14:1331-40.
Papakonstantinou E, Adonakis G. Management of pre-, peri-, and post-menopausal abnormal uterine bleeding: When to perform endometrial sampling? Int J Gynaecol Obstet. 2022;158(2):252-9.
Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.
de Medeiros SF, Yamamoto MM, Barbosa JS. Abnormal bleeding during menopause hormone therapy: insights for clinical management. Clin Med Insights Womens Health. 2013;6:13-24.
Spencer CP, Cooper AJ, Whitehead MI. Management of abnormal bleeding in women receiving hormone replacement therapy. BMJ. 1997;315(7099):37-42.
Hillard TC, Siddle NC, Whitehead MI, Fraser DI, Pryse-Davies J. Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis. Am J Obstet Gynecol. 1992;167(1):1-7.
Thomas AM, Hickey M, Fraser IS. Disturbances of endometrial bleeding with hormone replacement therapy. Hum Reprod. 2000;15 Suppl 3:7-17.
Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387-95.

Note: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person's circumstances and should always be discussed with that person's own healthcare provider. This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the ��ݮ��Ƶ.

Content updated 25 January 2024

Breast Cancer and Menopause

2020-04-27T00:00:00+10:00

Key Points

Menopause/menopausal symptoms in women with breast cancer have a significant negative impact on quality of life, with both short- and long-term health consequences.
Management of menopause in women with breast cancer is directed at relieving troublesome symptoms and minimising risks of cardiovascular disease, osteoporosis and breast cancer recurrence.
Menopausal hormone therapy after breast cancer is not usually recommended, regardless of the hormone receptor status of the tumour.
A variety of non-hormonal therapies for vasomotor symptoms have been investigated.
The safety of botanicals and phytoestrogens in breast cancer survivors is unclear.

AMS Breast Cancer and Menopause 146.46 KB

Introduction

Menopause/menopausal symptoms in women with breast cancer (BC) have a significant negative impact on quality of life, with both short- and long-term health consequences, and can affect BC treatment adherence. Menopause/menopausal symptoms in women with BC may be associated with (1) natural menopause occurring concurrently with a BC diagnosis, (2) recurrence of menopausal symptoms following cessation of menopausal hormone therapy (MHT) upon breast cancer diagnosis, (3) risk-reducing bilateral oophorectomy, chemotherapy or ovarian suppression secondary to gonadotropin releasing hormone (GnRH) analogues in premenopausal women, and/or (4) endocrine adjuvant therapy with tamoxifen or aromatase inhibitors¹.

Women with breast cancer, especially younger women, experience more severe menopausal symptoms than women without breast cancer² . The spectrum of symptoms is similar to usual age menopause (See AMS information sheet What is menopause?) and a study of 843 Australian women indicated that most women aged 50-69 years had persisting vasomotor, psychosocial, physical and sexual symptoms at 6 years post BC diagnosis despite having ceased adjuvant endocrine therapy³.

Women with BC may be at increased risk of cardiovascular disease (CVD). A systematic review assessing CVD mortality in women with BC reported that 9.4-10.4% died of CVD compared to 7.4-7.5% women without BC⁴. Multiple factors may influence CVD risk including the indirect/ direct effects of therapies including chemotherapy, radiotherapy, adjuvant endocrine therapies, lifestyle changes and weight gain accompanying BC diagnosis. The ten-year predicted CVD risk was greater than or equal to BC risk recurrence in a study of 415 women with BC, mean age 60 years⁵. Osteoporosis and fracture risk is also increased in women with BC, the greatest bone loss observed in younger women treated with GnRH analogue + aromatase inhibitor⁶. Adjuvant endocrine therapy, vitamin D deficiency and increased falls risk secondary to chemotherapy-induced neuropathy are some of the factors which contribute to osteoporosis risk⁶. Oestrogen depletion due to aromatase inhibitors is associated with accelerated bone loss which predisposes to increased fracture risk. In contrast, tamoxifen in postmenopausal women acts as an oestrogen on bone and retards bone resorption and reduces fracture risk.

Management of menopause in women with breast cancer is directed at relieving troublesome symptoms and minimising risks of cardiovascular disease, osteoporosis and breast cancer recurrence.

Diagnosis of menopause

The diagnosis of menopause is obvious after bilateral oophorectomy or where menopause occurred prior to BC diagnosis. However, in premenopausal women the diagnosis of menopause following BC chemotherapy can be difficult especially with concurrent tamoxifen therapy. FSH levels can be difficult to interpret in the women receiving tamoxifen, since, in contrast to its action in premenopausal women, tamoxifen partially suppresses gonadotrophins in the postmenopausal woman⁷. A model combining anti-mullerian hormone levels with age has been proposed to assist with the prediction of amenorrhoea post-chemotherapy⁸; however, validation in the real world setting is lacking.

Management of Menopause

Vasomotor symptoms

Although oestrogen containing MHT is the most effective therapy for vasomotor symptoms, there is conflicting evidence regarding safety of MHT after BC and it is not recommended, regardless of the hormone receptor status of the tumour. Clinical trials of MHT in women with early BC indicated that BC recurrence was increased after 2 years average follow-up in the HABITS study⁹ (Relative hazard [RH] = 3.3, 95% confidence interval [CI] = 1.5 to 7.4) but not after 4 years of follow-up in the Stockholm study¹⁰ (RH = 0.82, 95% CI = 0.35 to 1.9). These differences may relate to differences in progestogen exposure (continuous in HABIT and sequentially every 1-3 months in Stockholm), less tamoxifen use and higher rate of node positive patients in the HABITS trial¹⁰. Results from the LIBERATE trial indicated an increased risk of BC recurrence with tibolone therapy BC survivors (overall RR 1.40 95%CI 1.14-1.70)¹¹ regardless of whether the tumour was oestrogen and/or progesterone receptor positive. Although, the recurrence risk may be less in women with oestrogen receptor negative cancer¹¹. Historically, high dose progestogen therapy was used as adjuvant therapy. As MHT is not generally recommended, a variety of non-hormonal therapies for vasomotor symptoms have been investigated (see AMS information sheets Nonhormonal treatments for menopausal symptoms and Complementary and herbal therapies for hot flushes). Findings from a recent comparative analysis¹² are shown in Figure 1, indicating that the non-hormonal SSRIs/ SNRIs and neuroleptic agents (including gabapentin and pregabalin) had the greatest efficacy; whereas botanicals, magnesium and Vitamin E were comparable to placebo. These findings are consistent with recommendations of the North American Menopause Society (NAMS) position statement which also recommended cognitive behavioural therapy and hypnosis as treatment options (http://www.menopause.org/docs/default-source/professional/2015-nonhormonal-therapy-position-statement.pdf). The safety of botanicals and phytoestrogens in BC survivors is unclear. Compounded bioidentical hormone preparations may contain oestrogens and progestogens and their safety in BC is unknown.

Urogenital symptoms

Up to 75% of women with BC report at least one urogenital symptom if asked; however, many women do not raise this issue. Urogenital symptoms were considered to have the highest prevalence of “unmet need”¹³. Chemotherapy, aromatase inhibitor treatment and smoking are risk factors for urogenital symptoms. Vaginal oestrogens are the most effective treatment for urogenital symptoms; however, the use of these agents by women with BC, especially those taking aromatase inhibitors, is controversial. Recommendations from NAMS (https://www.menopause.org/docs/default-source/professional/management_of_genitourinary_syndrome_of_menopause.pdf) and the American College of Obstetricians and Gynaecologists (https://www.acog.org/-/media/Committee-Opinions/Committee-on-Gynecologic-Practice/co659.pdf?dmc=1&ts=20190527T0539259779) regarding management are:

(a) comprehensive assessment including history and physical examination

(b) counselling with validation and explanation of symptoms

(d) Long term safety and efficacy data are lacking for laser therapy (See AMS fact
sheet Vaginal laser therapy)

(e) For women taking adjuvant endocrine therapy who have an inadequate response
     with non-hormonal agents, discussion with the women, her oncologist and an
     individualised risk assessment is required for consideration regarding use of vaginal
     oestrogen. The use of intravaginal oestrogens with tamoxifen is of less concern
   compared to that in women taking aromatase inhibitors.

The safety of ospemifene, intravaginal DHEA and intravaginal testosterone is unknown in women with BC.

Lifestyle

Weight gain of 2.3-5kg occurs following BC diagnosis/ treatment and is multifactorial¹⁴. Excess weight is associated with increased BC recurrence. In overweight women, weight loss may assist with control of vasomotor symptoms and reduce CVD risk (see AMS information sheet Weight management and healthy ageing).

Bone health

Assessment of fracture risk is important for all women diagnosed with BC due to the negative impact of cancer therapies on bone health. A position statement⁶ , co-authored by the ��ݮ��Ƶ, recommends a comprehensive assessment of bone health including history to identify additional risk factors and investigations including biochemistry (serum electrolytes, liver function, 25OH Vitamin D, TSH, calcium, magnesium and phosphate), bone densitometry (DXA) and plain thoracolumbar Xrays (or VFA as part of DXA). Management should be directed at optimising dietary calcium intake (1000-1200mg/day), weight bearing exercise and vitamin D. Anti-resorptive therapy may be required in the setting of (i) prevalent or incident fragility fracture (ii) T score < -2.0 or significant bone loss.

Contraception

Pregnancy should be avoided during active treatment for BC. Systemic hormonal contraception (including oral, vaginal rings, subdermal or intrauterine) is not recommended¹⁵. The copper T IUD is recommended as a safe and effective form of contraception for women with BC. IUDs are 99.2% effective and provide contraception for 10 years¹⁵. Barrier and natural methods can be used although are less effective.

Figure 1: Calculated comparative efficacy (with 95% confidence interval) in reduction of hot flush frequency. Red dotted line indicates calculated placebo value and blue point indicates tibolone. Data derived from¹².

References

Vincent AJ. Management of menopause in women with breast cancer. Climacteric. 2015;18(5):690-701.
Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of Life, Fertility Concerns, and Behavioral Health Outcomes in Younger Breast Cancer Survivors: A Systematic Review. Journal of the National Cancer Institute. 2012;104(5):386-405.
Davis SR, Panjari M, Robinson PJ, Fradkin P, Bell RJ. Menopausal symptoms in breast cancer survivors nearly 6 years after diagnosis. Menopause. 2014;21(10):1075-1081 1010.1097/GME.0000000000000219.
Gernaat SAM, Ho PJ, Rijnberg N, et al. Risk of death from cardiovascular disease following breast cancer: a systematic review. Breast Cancer Research and Treatment. 2017;164(3):537-555.
Bardia A, Arieas ET, Zhang Z, et al. Comparison of breast cancer recurrence risk and cardiovascular disease incidence risk among postmenopausal women with breast cancer. Breast Cancer Res Treat. 2012;131(3):907-914.
Grossmann M, Ramchand SK, Milat F, et al. Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the ��ݮ��Ƶ and the Clinical Oncology Society of Australia. Clinical Endocrinology. 2018;89(3):280-296.
Lonning PE, Johannessen DC, Lien EA, Ekse D, Fotsis T, Adlercreutz H. Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. J Steroid Biochem Mol Biol. 1995;52(5):491-496.
Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Human Reproduction Update. 2014;20(3):370-385.
Holmberg L, Anderson H. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet. 2004;363(9407):453-455.
von Schoultz E, Rutqvist LE, Stockholm Breast Cancer Study G. Menopausal hormone therapy after breast cancer: the Stockholm randomized trial.[see comment]. Journal of the National Cancer Institute97(7):533-5. 2005.
Kenemans P, Bundred NJ, Foidart JM, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009;10(2):135-146.
Li T, Yang J, Lv Y, et al. Quantitative comparison of drug efficacy in treating hot flashes in patients with breast cancer. Breast Cancer Research and Treatment. 2019;173(3):511-520.
Yoon J, Malin JL, Tao ML, et al. Symptoms after breast cancer treatment: Are they influenced by patient characteristics? Breast Cancer Research and Treatment. 2008;108(2):153-165.
Vance V, Mourtzakis M, McCargar L, Hanning R. Weight gain in breast cancer survivors: Prevalence, pattern and health consequences. Obesity Reviews. 2011;12(4):282-294.
WHO. Medical eligibility criteria for contraceptive use Fifth ed. 20 Avenue Appia, 1211 Geneva 27, Switzerland: WHO Press, World Health Organization,; 2015.

Note: Medical and scientific information provided and endorsed by the ��ݮ��Ƶ might not be relevant to a particular person's circumstances and should always be discussed with that person's own healthcare provider. This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the ��ݮ��Ƶ.

Content updated September 2019

Calcium Supplements

2021-09-27T00:00:00+10:00

Key points

The recommended daily intake of calcium as recommended by Healthy Bones Australia (formerly Osteoporosis Australia) is 1300mg daily for women over the age of 50 and men over the age of 70, and 1000mg daily for other adults. Ideally most of this should be from dietary sources
Calcium supplements result in a marginal reduction in fracture risk, with evidence considered weak and inconsistent
The routine use of calcium supplements is not recommended
Whether calcium supplements lead to an increased risk of cardiovascular disease is unclear; if dietary calcium is inadequate then calcium supplements containing 500-600mg daily can be used
Calcium citrate is the preferred supplement with co-existent proton pump inhibitor or H2 antagonist use

AMS Calcium Supplements283.7 KB

Background

Osteoporotic fractures are a common problem worldwide and are associated with increased morbidity and mortality. Calcium is a major component of the skeleton and traditionally calcium supplements have been considered an integral part of osteoporosis management. Furthermore, most studies of osteoporosis therapies have been performed with the use of concurrent calcium supplements. In recent years, the role of calcium supplements has been controversial, particularly whether they lead to an increased risk of cardiovascular disease.

Calcium and fracture risk

Multiples studies have addressed the effect of calcium supplements with or without Vitamin D on fracture risk. While several studies shown a benefit on bone mineral density, the results on fracture reduction are conflicting (1,2,3). A meta-analysis of 17 trials with fracture as the primary outcome showed a modest relative risk reduction of borderline statistical significance (4). In a systematic review of 26 trials (5), there were again small and inconsistent beneficial reductions in fracture risk. Because of the minimal, if any, reduction in fracture risk, it means large numbers of patients would need to be treated to prevent a single fracture.

The conflicting results have been attributed to differences in their definitions of fracture and study designs, study bias and the populations studied (6). The beneficial effects of calcium and Vitamin D appear to be greater in individuals who are hospitalized or institutionalized compared to those in the community (7).

Which supplements are available?

Calcium carbonate (Caltrate®) and calcium citrate (Citracal ®) are the most widely available supplements. Calcium carbonate is better absorbed when taken with meals. It is not well absorbed however in patients with achlorhydria (low acid environment); calcium citrate is therefore preferred as a first line option for patients taking proton pump inhibitors or H2 blockers.

Side effects

High doses of calcium supplements may result in the formation of kidney stones. There is no evidence of an increased risk of nephrolithiasis from high dietary calcium intake. In the Women’s Health Initiative, women on calcium and Vitamin D supplements reported a higher rate of urinary tract stone formation compared to placebo (8). Gastrointestinal side effects such as nausea, vomiting and constipation have also been reported.

Calcium supplements and cardiovascular disease

In 2008, the Auckland calcium study reported an increased risk of myocardial infarction in post-menopausal women taking calcium supplements for 5 years compared to placebo (9). Of note, women were taking 1000mg of elemental calcium, 10% of the study population were > 80 years old at baseline and cardiovascular disease was not the primary endpoint. Vascular calcification is one postulated mechanism behind the increased cardiovascular risk.

The Women’s Health Initiative which randomized 36,282 women to calcium supplements (1000mg) and Vitamin D (400 IU) daily or placebo showed no increase in myocardial infarction in the calcium supplement group (8). However, 54% of the study population were already taking personal calcium supplements which were not part of the study protocol (10).

Subsequently, several meta-analyses including re-analysis of the WHI (including only women who were not taking calcium supplements at baseline) have been published with conflicting data (10,11,12). At present this topic remains a source of debate and there is insufficient evidence to declare one way or the other whether calcium supplements increase myocardial infarction or not. In light of the modest potential fracture benefit and possible cardiovascular risk, widespread use of supplements is not recommended.

What is clear is that calcium from dietary sources do not lead to an increased cardiovascular risk. Healthy Bones Australia recommends the optimal calcium intake to be 1000mg in adults > 19 years and 1300mg daily in post-menopausal women and men over 70. Most of this should be obtained through dietary sources. If dietary sources are inadequate, then supplements in the order of 500 – 600mg daily can be used. It is also recommended that calcium intake should not exceed more than 2000mg daily.

Useful links for calcium content in food:

https://healthybonesaustralia.org.au/your-bone-health/calcium/

https://www.osteoporosis.foundation/educational-hub/topic/calcium/list-of-calcium-content-of-common-foods

References

Silk LN et al. The Effect of Calcium or Calcium and Vitamin D Supplementation on Bone Mineral Density in Healthy Males: A Systematic Review and Meta-Analysis. International Journal of sport nutrition and exercise metabolism 2015; 25: 510-524
Boonen S et al. Addressing the musculoskeletal components of fracture risk with calcium and Vitamin D: A Review of the Evidence. Calcific Tissue Int Clin Endo 2006;78:257-270
Tai V et al Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;h4183
Tang et al. Use of calcium or calcium in combination with Vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007;370: 657-666
Bolland M et al. Calcium intake and risk of fracture. BMJ 2015; 351:h4580
Chiodini I et al. Calcium supplementation in osteoporosis: useful or harmful? European Journal of Endocrinology 2018;178:D13-D25
Chung M et al. Vitamin D with or without calcium supplementation for the prevention of cancer and fractures: an updated meta-analysis for the US Preventive Services Task Force. Ann Int Med 2011;155:827
Jackson RD et al. Calcium and Vitamin D supplementation and the risk of fractures. NEJM 2006;354:669-683
Bolland MJ et al. Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial. BMJ 2008 336: 262-266
Bolland MJ et al. Calcium supplements with or without Vitamin D and risk of cardiovascular events; reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 2011;342:d2040
Wang L et al. Systematic Review: Vitamin D and Calcium supplementation in the prevention of Cardiovascular events. Annals of Internal Medicine 2010;152:315-323
Harvey NC et al. Calcium and Vitamin D supplementation are not associated with risk of Incident Ischemic Events or Death: Findings from the UK Biobank Cohort. J Bone and Mineral Res. 2018; 33:808

Note: Medical and scientific information provided and endorsed by the Australasia Menopause Society might not be relevant to particular person's circumstances and should always be discussed with that person's own healthcare provider. This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the ��ݮ��Ƶ.

Content updated September 2021

Combined Menopausal Hormone Therapy (MHT)

2018-09-12T23:00:00+10:00

Key Points

MHT is the most effective treatment for hot flushes and night sweats.
Only women with an intact uterus need the addition of a progestogen.
The risks are small in most women within 10 years of their final menstrual period.
Non-oral routes of administration have fewer risks than oral preparations.
See AMS information sheet AMS Guide to Equivalent MHT/HRT Doses for a list of products available in Australia and AMS Guide to Equivalent MHT/HRT Doses New Zealand only.

AMS Menopause Combined MHT324.43 KB

The menopause is the final menstrual period and usually happens between the ages of 45 and 55 years. Around this time, women may experience symptoms such as hot flushes, sweating, vaginal dryness, loss of libido, irritability, sleep disturbance and muscle/joint pains. Oestrogen therapy is the most effective means of treating many of these symptoms. It will also prevent bone loss.

In a woman with an intact uterus, unopposed oestrogen therapy increases the risk of endometrial hyperplasia and cancer (1). Therefore, women who have not had a hysterectomy should take a progestogen as well to provide endometrial protection. Note that there is no therapeutic advantage of prescribing progestogen (either a progestin or natural progesterone) to women who have had a hysterectomy, (with the possible exception of women with symptomatic residual intra-peritoneal endometriosis) (2). In fact, there is a distinct disadvantage in terms of increased breast cancer and thrombotic risk and adverse changes in cardiovascular risk factors (3). (See information sheet on Risks and Benefits of MHT/HRT)

Combined menopausal hormone therapy may be given as "cyclical", where the oestrogen is given daily and the progestogen is given for 10-14 days of the month, or "continuous" where both oestrogen and progestogen are given daily. "Cyclical" produces withdrawal vaginal bleeds whereas "continuous" should not.

As a general rule, cyclical hormone therapy is used for a woman who is in the menopausal transition and is having some irregular spontaneous menses or is very recently postmenopausal, but it can be continued longer if preferred. Continuous hormone therapy is a convenience often preferred by older women. Early introduction of continuous MHT close to the menopausal transition may lead to irregular, unscheduled breakthrough bleeding. Breakthrough bleeding may occur in the first six months of any MHT regimen but any unscheduled bleeding after that should be investigated.

Combination packs of either cyclical or continuous preparations are available. These improve medication compliance and ensure reliable endometrial exposure to progestogen. If, for reasons of intolerance to either the formulation or the mode of delivery, it is thought necessary to "mix and match" oestrogen and progestogen preparations, it is important to emphasise to the patient that reliable endometrial protection depends upon sufficient progestogen exposure (4).

Types of oestrogens

Oestrogens are available as tablets, skin patches, and gels.
Patches or gels may be better for those with gut absorption problems.
Patches or gels are also better for those who have high triglyceride concentrations or who are at risk of venous thromboembolic disease (5). This includes those who are overweight and smokers.
Vaginal oestrogen in creams, pessaries or tablets is available for vaginal dryness or dyspareunia.

Types of progestogens

The term "progestogen" encompasses both natural progesterone and synthetic preparations which act on the progesterone receptor. The term "progestin" is used purely for the synthetic preparations. Progestins may be derived from progesterone or other steroids (such as testosterone) and most have other biological effects, such as on either the androgen receptor, the glucocorticoid receptor or the mineralocorticoid receptor, in addition to their progestogenic effects (6).
Progestogens are mostly taken orally. The only progestogen which is reliably absorbed through the skin is norethisterone, used in the combined MHT patches. Progesterone creams are not reliably absorbed and do not confer adequate endometrial protection.
Micronised progesterone capsules are a form of natural or “body-identical” progesterone recently available in both Australia and New Zealand.
An alternative method is to deliver the progestogen directly to the endometrium using the levonorgestrel containing intrauterine system (Mirena).
There is no evidence that either progesterone troches or progesterone cream confer adequate endometrial protection (7).

Other MHT

Tibolone is a synthetic progestogenic hormone which, once metabolized, acts like oestrogen, progestogen and testosterone (see AMS information sheet on Tibolone as menopausal hormone therapy).
A selective oestrogen receptor modulator (SERM) called bazedoxefine, has been combined with conjugated equine oestrogens in what is referred to as a tissue selective oestrogen complex (TSEC) with the trade name Duavive™. It is used to prevent osteoporosis and treat menopausal symptoms without the need for a progestogen in women with an intact uterus and at least 12 months since last menses. (See AMS information sheet SERMs – their role in menopause management).
Testosterone – is sometimes added to MHT and may improve libido and energy in some women (see AMS information sheet on Sexual difficulties in the menopause).

Before prescribing

A full history and clinical examination should be done, exploring possible contraindications or relative contraindications to MHT or to specific formulae.
Mammograms, breast checks and cervical screening should be up to date in all women over 50 years whether they are taking MHT or not.
Any unexplained vaginal bleeding should be investigated.
Ensure the patient understands benefits and risks (see Information sheet on Risks and Benefits of MHT/HRT).

Choice and adjustment of therapeutic regimens

The choice of oestrogen dose depends upon how a woman's symptoms respond and on her well-being, not on measurement of blood levels.
Transdermal preparations are preferred for women with malabsorption, risk or past history of DVT, migraine, untreated hypertension and significant liver disease.
Most problems with intolerance are related to the progestogen. These include mood changes, bloating, headache, and mastalgia. These symptoms may benefit from a change to a different progestogen formulation (eg micronised progesterone) or mode of delivery.
Progestogens should be taken cyclically for 10-14 days each month, aiming for a predictable monthly bleeding pattern, or continuously, which is designed to give no bleeding. However irregular bleeding is common with all regimens, particularly during the first three to six months of use. After this time, investigation with ultrasound +/- hysteroscopy and endometrial sampling is indicated. An adjustment of the progestogen to oestrogen dose ratio may fix the problem.
For women who cannot tolerate progestogen tablets, an alternative is to try the levonorgestrel intrauterine system (Mirena), although some systemic absorption occurs with this device.

The benefits of MHT

MHT is the most effective treatment for hot flushes and night sweats.
MHT also effectively treats vaginal dryness.
Reducing menopausal symptoms with MHT may improve quality of life.
MHT reduces the risk of postmenopausal bone fracture, including hip fracture (3).
MHT use is not associated with weight gain (8).

Managing the risk

Regular breast checks and screening mammograms should be performed in women over 50 years whether they are taking MHT or not.
MHT should be reviewed annually by the woman in consultation with her doctor. Personal benefits versus risk should be discussed.
If a woman using MHT develops symptoms suggesting DVT or stroke, she should stop the MHT and seek medical attention (see AMS information sheet on Venous thrombosis/Thromboembolism and menopausal treatments).
Oral MHT increases the risk of venous thromboembolism. In women less than 60 years the risk is low. The risk increases with age and other risk factors such as obesity, previous thromboembolism, smoking and immobility. The risk is less with the use of transdermal preparations and also with the use of oestrogen alone (5).

Continuation or cessation of combined MHT

The dose and duration of MHT should be consistent with treatment goals, such as symptom relief, and should be individualized (9).
Women who go through menopause before 45 years are advised to take MHT until the average age of menopause, i.e. around 50 years. The discussion and decision to continue MHT is then the same as it is for women who are experiencing menopause at the usual age and considering starting MHT (see AMS information sheet on Spontaneous premature ovarian insufficiency).
The risk of breast cancer is primarily associated with combined oestrogen/progestogen therapy and related to the duration of use. The risk of breast cancer attributable to combined MHT is small and decreases after treatment is stopped. Oestrogen alone has not been shown to increase breast cancer risk in high quality randomized controlled trials.
Oral MHT increases the risk of stroke and the risk increases with age. Stroke risk is not significantly altered in women younger than 60 years with normal blood pressure. The risk may be less with the use of oestrogen gel or skin patches.
Cessation of MHT is associated with increased cardiovascular and cerebrovascular events and increased risk of fracture (10, 11).

September 2018

References

Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database of Systematic Reviews. 2012;8:CD000402.
Al Kadri H, Hassan S, Al-Fozan HM, Hajeer A. Hormone therapy for endometriosis and surgical menopause. Cochrane Database of Systematic Reviews. 2009(1):CD005997.
Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013 Oct 2;310(13):1353-68.
Schindler AE. Progestogen deficiency and endometrial cancer risk. Maturitas. 2009 Apr 20;62(4):334-7.
Canonico M, Plu-Bureau G, Lowe GDO, Scarabin P-Y. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008 May 31;336(7655):1227-31.
Stanczyk FZ. All progestins are not created equal. Steroids. 2003 Nov;68(10-13):879-90.
Elshafie MAA, Ewies AAA. Transdermal natural progesterone cream for postmenopausal women: inconsistent data and complex pharmacokinetics. J Obstet Gynaecol. 2007 Oct;27(7):655-9.
Davis SR, Castelo-Branco C, Chedraui P, et al. Understanding weight gain at menopause. Climacteric. 2012 Oct;15(5):419-29.
de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013 Jun;16(3):316-37.
Mikkola TS, Tuomikoski P, Lyytinen H, et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab. 2015 Dec;100(12):4588-94.
Karim R, Dell RM, Greene DF, Mack WJ, Gallagher JC, Hodis HN. Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization. Menopause. 2011 Nov;18(11):1172-7.

This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by ��ݮ��Ƶ Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the ��ݮ��Ƶ.

Content updated 12 September 2018

Complementary Medicines and Therapies for Hot Flushes

2025-04-24T12:54:00+10:00

Key points

There have been many studies of complementary and herbal medicines for the relief of menopausal symptoms.
Any product used for the treatment of menopausal symptoms should have been shown in clinical studies to be safe and effective.
There is currently insufficient evidence to support the use of herbal therapies.
Compounded bioidentical hormonal preparations are not recommended due to major concerns about the safety and efficacy of these products.
No complementary therapy is as effective as oestrogen therapy for menopausal symptoms.

AMS Complementary Medicines and Therapies for Hot Flushes268.65 KB

Many women experience hot flushes and night sweats around the time of menopause. Menopausal hormone therapy (MHT) has been proven to be effective in alleviating these symptoms.¹ However, some women choose to explore complementary medicines and therapies (CM&T) for relief of symptoms. There have been many studies on CM&T; some have suggested benefits, and others have shown no benefit. It can be difficult for consumers and doctors to interpret this mixed information.² This information sheet provides a brief overview of the current evidence for the use of CM&T.

CM&T are sometimes referred to as “natural” and may be derived from plants and other sources. Some people believe that these products are safer than prescription products. However, scientific studies of these compounds do not always support this belief.² Extracts from plants and other so-called “natural” products may actually cause harm and interact with prescribed medicines.³ They do not necessarily act like the hormones normally produced by women. Some over-the-counter treatments, including plant extracts, are not subject to the rigorous testing for content, safety and effectiveness that prescription treatments are subject to. Herbal products may contain heavy metals, illegal ingredients and toxic chemicals as well as naturally occurring organic toxins.

Any product used for the treatment of menopausal symptoms should have clinical studies showing it to be effective. This usually requires a placebo-controlled trial or a head-to-head comparison with a known effective treatment, or both. The placebo comparison is important because there is often a temporary placebo that commonly lasts around three months.¹

Unless the product is tested for more than three months, it is not possible to say it is truly effective for menopausal symptoms. This short-term placebo effect is quite different from the prolonged improvement in menopausal symptoms demonstrated by treatments such as MHT. MHT reduces hot flushes by around 90% and continues to be effective for as long as they are used.⁴Prescription drugs cannot be licensed until they have been shown to be safe and effective. This is not the case for over-the-counter remedies for menopausal symptoms.

The AMS advocates that all therapies, whether prescription or alternative, should not be used unless there is good research evidence for their effectiveness and safety over the short and long term.

CM&T use in Australia

In a national representative sample of 10,011 Australian women aged 59-64 years:⁵

39% of menopausal women consulted CM&T practitioners.
75% used self-prescribed CM&T.
95% consulted general practitioners (GP) and 50% consulted specialists during the previous year, and 12% were current menopausal hormone therapy (MHT) users.

Similarly, a cross-sectional questionnaire-based study of 2020 Australian women aged 40-65 years living independently in the community found that the prevalence of CM&T use to manage menopausal vasomotor symptoms (VMS) was 13.22%.⁶

Specific herbal and botanical therapies

Black cohosh (Cimicifuga racemosa or Actaea racemosa)

Specific extracts of black cohosh (isopropanolic), and higher therapeutic doses may improve menopausal symptoms, including hot flushes, as shown in a recent systematic review and meta-analysis.⁷ It should be noted that most of the included studies were conducted over short time frames (i.e. 3-6 months) and on small numbers of patients. In addition, although many were placebo-controlled trials, no studies compared black cohosh to conventional MHT.

There were originally reports of liver toxicity from the use of black cohosh.⁸ A review of the 69 cases of suspected black cohosh-induced liver disease concluded that data does not support a direct causal relationship, with no signal of safety concern.⁹Another meta-analysis found no evidence of black cohosh adversely affecting liver function, although studies were only up to 6 months of treatment.¹⁰

Phytoestrogens (including red clover, below)

A wide range of products containing plant or phytoestrogens, including soy products, are available as over the counter remedies for hot flushes. The active product of these is thought to be isoflavones which bind to the oestrogen receptor. Isoflavones have a greater affinity for ER-β than for ER-α and possess both oestrogen agonist and antagonist properties. There are study limitations and differences in the interventions and the findings are mixed. Some studies demonstrated efficacy of soy in reducing VMS or severity and others showing no benefit from soy compared to placebo.¹¹ Efficacy of soy may be influenced by whether an individual is able to metabolize the soy isoflavone daidzein to the more potent phytoestrogen, equol. Around 20-30% of Caucasians (compared to 40-70 % of Asians) are equol producers.¹² Equol supplements are not readily available in Australia. Compared to placebo, equol supplementation was found to be superior to placebo for reducing VMS frequency in 3 of the 5 trials assessed in a 2019 systematic review and meta-analysis.¹³

Updated information by the Cancer Council of Australia, influenced by the World Cancer Research Fund (WCRF) state that the available evidence suggests that soy and other isoflavone-containing foods are unlikely to increase cancer risk, and recommend that people, including those who have been diagnosed with breast cancer, who consume soy foods, should continue to do so.^14,15

Red clover (Trifolium pratense)

Specific extracts of red clover may be useful in reducing the daily frequency of hot flushes, particularly in post-menopausal women, if taken for a period of 12 weeks and with higher doses of isoflavones (≥80 mg/day,) and when the formulations contained a higher proportion of biochanin A.¹⁶

Preliminary evidence suggests there may be some benefit from use of red clover in reducing cholesterol and low-density lipoprotein (LDL).¹⁷

Siberian rhubarb (Rheum rhaponticum)

A systematic review and meta-analysis of the standardised extract of Rheum rhaponticum root, ERr 731^® significantly reduced the Menopause Rating Scale score compared with control.¹⁸Ffurther research is needed to establish long-term efficacy and safety.¹¹

St John’s wort (Hypericum perforatum)

Combined with black cohosh, St John’s Wort can be effective for menopausal mood symptoms. A small, randomised control-trial (n=301) compared isopropanolic black cohosh extract and ethanolic St John’s wort against a placebo. Scores on the Menopause Rating Scale decreased by 50% in the treatment group compared to 19% in the placebo group. Depression also significantly decreased compared with placebo.¹⁹

It is important to note that this therapy may interact with many prescription medicines. A lack of long-term safety data limits recommendations for its use.¹¹

Evening primrose oil

Very few studies have addressed whether evening primrose oil improves hot flushes. Existing data shows no benefit in one study,²⁰ and another small study showed a reduced frequency and severity of night sweats, but not hot flushes, compared to placebo at a dose of 1000 mg twice a day for 8 weeks (n=170).²¹ Evening primrose oil lowers the seizure threshold in people with epilepsy and interferes with the actions of anti-epileptic medication.³

Flaxseed

Two small recent studies have shown flaxseed (also known as linseed) may be beneficial in improving hot flushes, night sweats and vaginal dryness in perimenopausal women, with the longest study conducted over 8 months.^22,23 More evidence is needed before flaxseed can be recommended for use.

Ashwaganda (Withania somnifera)

Ashwaganda is an herbal product used in Ayurvedic medicine for its supposed adaptogenic and anti-stress properties. Only one small study, undertaken in 100 women over only 8 weeks, looked at its use for management of perimenopausal symptoms, with significant reductions in menopause symptom scores noted.²⁴

Importantly, the Therapeutic Goods Association (TGA) issued a safety advisory for Withania somnifera in 2024 due to reports of severe gastrointestinal symptoms and liver damage in patients taking the herb, several of whom required hospitalisation.²⁵ Use of medicines or herbal supplements containing Withania somnifera should be avoided in patients with existing or previous liver pathologies.²⁵

Non-herbal medicines and therapies

Vitamin E

Two very small and short-term studies have shown that Vitamin E (800 iu per day for 4 weeks) decreased the number of hot flushes by 1 per day when used by women who have had breast cancer (n=120),²⁶ and reduced the number of hot flushes by 2 per day in other women (400 iu vitamin E daily, n= 51).²⁷

Omega-3

Use of Omega-3 showed no difference in the frequency and severity of hot flushes, insomnia severity, sleep quality compared to placebo in a systematic review and meta-analysis (n=183).²⁸

Supplementation with omega-3 can improve the lipid profile of postmenopausal women,²⁹ and the Heart Foundation of Australia recommend fish oils as part of an adult diet to help lower the risk of coronary heart disease.³⁰

Cognitive behavioural therapy, hypnosis, yoga and non-prescription medicines

The AMS information sheet ‘Nonhormonal treatments for menopausal symptoms’ covers this.

Compounded bioidentical menopausal hormone therapy (including progesterone cream)

There is no evidence to support the efficacy or safety claims of compounded “bioidentical” hormones, or the superiority claims of these over conventional MHT. These products also pose the additional risks of variable purity and potency. All major national and international menopause societies have raised concerns about the safety and efficacy of these products and recommend that patients be counselled to avoid their use.³¹ The AMS information sheet Bioidentical hormones for menopausal symptoms has more information.

Other CM&T with little or no evidence of benefit in treating menopausal symptoms

Wild yam cream
Ginseng (Panax ginseng or Panax quinquefolius)
Maca (Lepidium Meyennii Walp or Lepidium peruvianum Chacon)
Pine bark (Pyncogenol)
Pollen extract
Magnesium
Combination botanical therapies
Homeopathy
Acupuncture

Updated April 2025

Additional Reading

Management of menopausal symptoms in women with a history of breast cancer | Cancer Australia
The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society Advisory Panel: https://pubmed.ncbi.nlm.nih.gov/37252752/
Memorial Sloan Kettering Cancer Center information on Integrative medicine including the “About Herbs” database. Note this is a USA website and not all of the products mentioned will be available in Australia: https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs/search

References

MacLennan AH et al. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004; 4:18.
Nedrow AJ et al. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 2006;166(14):1453-65.
Byard RW et al. What risks do herbal products pose to the Australian community? MJA 2017;206(2):86-90.
MacLennan AH. Evidence-based review of therapies at the menopause. International Journal of Evidence Based Healthcare 2009;7(2):112-23.
Peng et al. Complementary/alternative and conventional medicine use amongst menopausal women: results from the Australian Longitudinal Study on Women’s Health. Maturitas 2014; 79(3):340-42.
Gartoulla et al. Use of complementary and alternative medicines for menopausal symptoms in Australian women aged 40-65 years. MJA 2015; 203(3):146.
Castelo-Branco, C et al. Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence. Climacteric 2021; 24(2): 109–119. https://doi.org/10.1080/13697137.2020.1820477
Whiting PW et al. Black cohosh and other herbal remedies associated with acute hepatitis. MJA 2002;177(8):440-3.
Teschke R. Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review. Menopause 2010; 17(2): 426–440. https://doi.org/10.1097/gme.0b013e3181c5159c
Naser B et al. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause 2011;18(4):366-75.
“The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society” Advisory Panel (2023). The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023; 30(6): 573–590. https://doi.org/10.1097/GME.0000000000002200
Cui C et al. Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutrition reviews 2020; 78(2), 134–144. https://doi.org/10.1093/nutrit/nuz050
Daily J et al. Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Journal of medicinal food 2019; 22(2):127–139. https://doi.org/10.1089/jmf.2018.4265
World Cancer Research Fund / American Institute for Cancer Research. Wholegrains, vegetables and fruit and the risk of cancer [Internet]. London; 2018. Available from: https://www.wcrf.org/dietandcancer/exposures/wholegrains-veg-fruit
Information sheet: Soy & isoflavones | Cancer Council
Kanadys W et al. Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2021; 13(4), 1258. https://doi.org/10.3390/nu13041258)
Yigit E et al. Isoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomized placebo-controlled trial. Climacteric 2024; 1–7. Advance online publication. https://doi.org/10.1080/13697137.2024.2393121)
Dubey VP et al. Efficacy evaluation of standardized Rheum rhaponticum root extract (ERr 731 ^®) on symptoms of menopause: A systematic review and meta-analysis study. Journal of biomedical research 2024; 38(3):278–286. https://doi.org/10.7555/JBR.37.20230219
Uebelhack et al. Black cohosh and St Johns’ wort for climacteric complaints. Obstet Gyn 2006; 107(2):247-55.
Chenoy R et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994;308(6927):501-3.
Kazemi F et al. The Effect of Evening Primrose Oil Capsule on Hot Flashes and Night Sweats in Postmenopausal Women: A Single-Blind Randomized Controlled Trial. Journal of menopausal medicine 2021; 27(1), 8–14. https://doi.org/10.6118/jmm.20033
Dizaye K et al. Effects of flaxseed (Linum usitatissimum) on climacteric symptoms and clinical parameters in post-menopausal women: Flaxseed effects on menopause associated symptoms and biochemical parameters. Iraqi Journal of Pharmaceutical Sciences 2023; 32:257-265.
Shrivastava R et al. Effects of Flaxseed on Perimenopausal Symptoms: Findings From a Single-Blind, Randomized, Placebo-Controlled Study. Cureus 2024; 16(9): e68534. https://doi.org/10.7759/cureus.68534
Gopal S et al. Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study. The Journal of Obstetrics and Gynaecology Research 2021; 47(12): 4414–4425. https://doi.org/10.1111/jog.15030
https://www.tga.gov.au/news/safety-alerts/medicines-containing-withania-somnifera-withania-ashwagandha
Barton DL et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1998; 16(2): 495–500. https://doi.org/10.1200/JCO.1998.16.2.495
Ziaei S et al. The effect of vitamin E on hot flashes in menopausal women. Gynecologic and obstetric investigation 2007; 64(4): 204–207. https://doi.org/10.1159/000106491
Mohammady M et al. Effect of omega-3 supplements on vasomotor symptoms in menopausal women: A systematic review and meta-analysis. European journal of obstetrics, gynecology, and reproductive biology. 2018; 228:295–302. https://doi.org/10.1016/j.ejogrb.2018.07.008
Wang J et al. Does Omega-3 Fatty Acid Supplementation Have Favorable Effects on the Lipid Profile in Postmenopausal Women? A Systematic Review and Dose-response Meta-analysis of Randomized Controlled Trials. Clinical therapeutics 2023; 45(1): e74–e87. https://doi.org/10.1016/j.clinthera.2022.12.009
https://assets.contentstack.io/v3/assets/blt8a393bb3b76c0ede/blt30294411bd96bdd3/65ea8b022b979deb55896f8b/Summary_Evidence_FISH_FISH-OILS_FINAL.pdf
“The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 Jul 1;29(7):767-794. doi: 10.1097/GME.0000000000002028. PMID: 35797481.

Content Updated April 2025

Contraception

2022-07-26T11:04:47+10:00

Key Points

Contraception is required for 12 months after the final menstrual period (FMP) if the FMP occurs after the age of 50. If the FMP occurs before the age of 50, 24 months of contraception is required.
Oestrogen - based methods are not recommended over the age of 50 due to cardiovascular risks.
The Levonorgestrel IUD (Mirena®) provides effective management of heavy menstrual bleeding as well as contraception and can also be used as part of an MHT regimen
Women in a new relationship should be advised about the use of condoms to prevent sexually transmitted infections.
Women should be informed about the availability of the Emergency Contraceptive Pill without a prescription at pharmacies.

AMS Contraception357.93 KB

Fertility declines with age and available data suggest that spontaneous conception for women over age 50 is very rare (1). Pregnancy at the age of 45-49 results in a live birth rate of less than 2 per 1000, while over the age of 50 it is less than 1 per 2000. Despite the low risk in this age group, women should be counselled about the possibility of unintended pregnancy and advised about appropriate contraception.

Contraception is required for 12 months after the final menstrual period (FMP) if the FMP occurs after the age of 50 (2). If the FMP occurs before the age of 50, 24 months contraception is required.

Amenorrhea is common in perimenopausal women using progesterone-only contraception making it difficult to determine the date of her FMP. In this situation, for women age 50 or older, a single FSH measurement ≥30mI U/L will indicate that contraception will be required for a further 12 months, and can then be ceased. If the FSH is ≤30mIU/L, contraception should be continued for the next 12 months and FSH to be repeated to check if ≥30 at that time (3).

The choice of contraception is determined by several factors including the woman’s age, medical eligibility criteria (4), comorbid medical conditions, affordability, and personal choice. Oestrogen-containing methods are not recommended for women over the age of 50. Women of any age with contraindications to oestrogen, such as a history of breast cancer, thromboembolic disorders, complex migraines and heavy smokers should be offered non-hormonal or progestogen-only methods.

1. LONG-ACTING REVERSIBLE CONTRACEPTIVE METHODS (LARC)

(a) Levonorgestrel Intrauterine System (hormonal IUS)

(i) The Mirena IUD® is inserted into the uterus. It releases levonorgestrel (LNG) 52mg over 5 years (with extended use for contraception up to 10 years if inserted after age 45) (3). It works primarily by thinning the endometrium and thickening of the cervical mucus. It is a highly effective form of contraception (>99% efficacy) (4) and suitable for women with contraindications to oestrogen–containing methods.

Women should be warned of possible spotting and bleeding for the first few months. Some women experience progestogen side effects such as acne and mood changes.

The Mirena IUD is an excellent option for women around the perimenopause particularly if they are experiencing irregular heavy periods. It also provides endometrial protection for women using MHT; use should not be extended beyond 5 years at any age for this indication.

(ii) The Kyleena IUD® is similar to the Mirena® but releases a smaller dose of LNG (19.5mg) over 5 years. The IUD device itself is smaller than the Mirena and is most suitable for nulliparous women who don’t mind having a regular lighter period. Importantly it does NOT provide adequate endometrial protection for women on MHT and is not suitable for women experiencing heavy menstrual bleeding around the time of menopause.

In New Zealand, Jaydess® is the lower dose IUS, releasing 13.5mg of levonorgestrel over its use in 3 years.

(b) The Contraceptive Implant

The Implanon NXT® is available in Australia and is a 4cm single rod inserted under the skin of the inner non-dominant arm under local anaesthetic. It releases the progestogen etonorgestrel over a three-year period but can be removed earlier if required. It inhibits ovulation, thickens the cervical mucus and thins the endometrium. The Implanon is available on PBS in Australia.

In New Zealand the Jadelle® implant is fully funded. It consists of 2 small flexible silicon rods, each containing levonorgestrel 75mg.

The contraceptive implants provide highly >99% effective (5) and are cost-effective. Side effects can include irregular bleeding along with common progestogenic side effects (6). Contraceptive implants should not be used for endometrial protection in an MHT regimen.

(c) Copper-bearing IUD

The copper IUD is >99% effective. It is toxic to sperm and can prevent implantation of the fertilized egg. In Australia, three types of Copper IUD are available, Load375® and Copper TT380 Short® which last for 5 years and Copper TT380 Standard®, which is effective for 10 years. As there are no hormones, it is suitable for women concerned about hormone side effects or those with contraindications to hormonal methods.

The Copper IUD can cause heavier, longer and more painful periods. In Australia Copper IUDs are not PBS listed with a higher upfront cost that the hormonal IUDs. In New Zealand, Copper IUDs are subsidised and less expensive than the hormonal IUD.

2. MEDIUM ACTING CONTRACEPTION

(a) Depomedroxyprogesterone acetate (DMPA) injections

DMPA injections (Depo-Provera® and Depo-Ralovera®) are progestogen-only injections administered every 3 months into the gluteal or deltoid muscle. It prevents ovulation and is 99.8% (5) effective when used correctly. Most women are amenorrhoeic so it may be helpful for women with heavy menstrual bleeding. As it also suppresses oestrogen production, long term use may result in low bone density or osteoporosis (7). For this reason, it is also less preferred in women over age 45 (7, 8).

(b) The Vaginal Ring

The vaginal ring (NuvaRing®) is a soft silastic ring containing ethinyl oestradiol and etonorgestrel. It is inserted by the woman herself and left in place for 3 weeks, then removed for a week before a new ring is inserted. Women must remember to remove and replace the ring for it to be effective.

The vaginal ring works in a similar principle to the oral contraceptive pill but obviates the need for daily tablet taking. In perfect use the risk of pregnancy is <1% per year (5). The vaginal rings can be used ‘back-to-back’ for 3 months at a time, to prevent withdrawal bleeding. It can also provide better regulation of the menstrual cycle for women who experience breakthrough bleeding with combined oral contraceptive pill (COCP).

The vaginal ring has the same contraindications as COCP (see below). It is not PBS listed so the cost may be a deterrent for some women.

3. SHORT ACTING CONTRACEPTION

(a) The Combined Oral Contraceptive Pill (COCP)

The COCP contains both oestrogen and progestogen hormones. It works primarily by inhibiting ovulation but also thickens cervical mucus and thins the endometrium with >99% efficacy with perfect use (93% in typical use) (5). Active hormone pills can be taken continuously for up to 12 months to reduce menstrual blood loss. There is some data that suggest a reduction in the risk of ovarian and endometrial cancer with COCP use.

The COCP should not be used in women with contraindications to oestrogen (e.g. women with a history of breast cancer, VTE, migraine with aura and smokers over the age of 35 year). The COCP is associated with an increased risk of VTE by approximately 2-fold (8) (although the absolute risk for most women is very low). The COCP is not recommended for women over the age of 50 because of increased cardiovascular risk. For women with additional risk factors such an elevated BMI, a history of diabetes or hypertension, consideration should be given to cease the use of COCP at an earlier age.

(b) The progestogen-only pill (POP) or “minipill”

The progestogen-only pill contains a small dose of progestogen and primarily works by thickening cervical mucus. It can be used by women with contraindications to the use of oestrogen who prefer an oral method. There is no increased risk of thromboembolic events.

Most POPs must be taken within a three-hour time frame each day for it to be effective, although the newer Drospirenone-containing Mini-Pill (Slinda®) has a 24-hour window (10).

In New Zealand, Cerazette® is the only POP available and has a 12-hour window of use.

Similar to contraceptive implants, POPs should not be used for endometrial protection in an MHT regimen.

4. COITALLY DEPENDENT BARRIER METHODS

The barrier methods require ‘action’ with every act of sexual intercourse, which results in lower effectiveness in typical use than other contraceptive methods. Condoms, both male and female (now also referred to “external” and “internal” condoms respectively), are the only method of contraception that can prevent STIs.

(a) Contraceptive Diaphragm

The diaphragm Caya® is a barrier method which the woman inserts herself, to cover the cervix to prevent sperm reaching the uterus. It must be left in place for a minimum of 6 hours after intercourse to allow sperm to be killed off by the vaginal acidity. The single size diaphragm has a lifespan of two years; the manufacturer recommends the use of a lactic acid buffer gel with the diaphragm (note that spermicide is not available in Australia).

The diaphragm may be associated with urethal irritation and a risk of urinary tract infection (10). Some women find it difficult to insert and there is a risk of incorrect placement.

(b) Male Condom

The male condom is a fine latex or polyurethane sheath, worn on the erect penis. It can be used with a water-based lubricant which may be useful for women experiencing perimenopausal vaginal dryness.

Condoms have a relatively high failure rate in typical use (especially in ‘new users’) due to the need for consistent use and the risk of breakage, slippage or leakage (98% effective in perfect use and 88% in typical use) (4). Some men and some women believe they interfere with sexual pleasure.

(c) Female Condom

The female condom is a polyurethane sheath inserted into the vagina prior to intercourse. It is less commonly used than other forms of contraception. They are more expensive than male condoms and have a slightly higher failure rate. They can be purchased online at family planning clinics and also at some pharmacies. More information here: here

5. EMERGENCY CONTRACEPTION

Emergency contraception (previously known as “the morning after pill”) is used to prevent pregnancy after unprotected intercourse or contraceptive failure.

(a) Single 1.5mg levonorgestrel emergency contraceptive (LNG-ECP) tablet

The LNG-ECP contains 1.5mg levonorgestrel and is recommended for use up to 72 hours after unprotected intercourse; it has some effectiveness if taken up to 120 hours after unprotected intercourse. It is available over the counter without a prescription. It acts by preventing or delaying ovulation. It can be used by breastfeeding women and can be used multiple times in a cycle if needed.

(b) Single 30mg ulipristal acetate (UPA) tablet

Ulipristal acetate is a selective progesterone receptor modulator (SPRM) which works to prevent or delay ovulation even when the LH surge has begun. It can be used up to 120 hours after unprotected intercourse with superior efficacy to LNG-EC. Breastfeeding women are advised to express and discard breastmilk for one week after taking UPA. Women using progestogen containing contraception should seek medical advice on when to start or re-start the method after taking UPA as UPA can reduce the effectiveness of hormonal contraception.

(c) Copper IUD

If inserted within five days of unprotected intercourse, the copper IUD provides highly effective ongoing long-term contraception. However, it can be difficult to access within the appropriate time frame.

6. PERMANENT

(a) Tubal ligation or Salpingectomy (female sterilization)

Tubal ligation or salpingectomy are carried out under general anaesthetic either laparoscopically or during laparotomy. It may be appropriate for women undergoing laparoscopy for other reasons or at the time of a Caesarian Section. It may be appealing for women concerned about side effects of other contraceptive methods.

(b)Vasectomy (male sterilization)

Vasectomy is a surgical procedure, usually performed under local anaesthetic, during which the vas deferens is cut so that no sperm will enter the ejaculate. It allows the male partner to take responsibility for contraception. Couples should be advised ongoing contraception is required for 3 months after the procedure, at which time a follow-up semen analysis is performed to confirm azoospermia. There is a small risk of haematoma, infection, sperm granuloma and rarely post-vasectomy pain syndrome.

References

Trussell J et al. Sterility in a population with natural fertility. Population Studies 2010;39(2):269–86
Sauer MV. Reproduction at a advanced maternal age. Fertility Sterility. 2015; 103(5):1136-43
Faculty or Sexual and Reproductive Healthcare. FSRH Guideline for women aged over 40 years. Contraception for Women aged over 40 years. FSRH Clinical Effectiveness Unit; 2017(Amended 2019). https://www.fsrh.org/documents/fsrh-guidance-contraception-for-women-aged-over-40-years-2017/
Pearson S et al. Long Acting Reversible Contraceptives. AJGP 2022;51(4)
Faculty of Sexual & Reproductive Healthcare. UK medical eligibility criteria for contraceptive use. FSRH, 2019.
Sexual and Reproductive Health Experts Group. In: Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited;2020. Available online at:
https://tgldcdp.tg.org.au/guideLine?guidelinePage=Sexual+and+Reproductive+Health&frompage=etgcomplete (subscription required) (accessed March 2022)
Rocca ML et al. Safety and Benefits of Contraceptive Implants: A Systematic Review Pharmaceuticals (Basel). 2021; 14(6): 548
Albertazzi P et al. Bone Mineral Density and Depot medroxyprogesterone acetate. Contraception 2006; 73(6):577-83
Royal College of Obstetricians and Gynaecologists. Contraception for Women Aged Over 40 Years. In: Faculty of Sexual & Reproductive Healthcare Clinical Guidance, editor. 2010
Dragoman MV et al. A systematic review and meta‐analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynaecol Obstet.2018 Jun; 141(3): 287–294 https://doi.org/10.1002/ijgo.12455.
Bateson D et al. Drospirenone 4mg: A new progestogen only pill. Medicine Today 2021; 22(12):56-59
Allen RE. Diaphragm Fitting. Am Fam Physician. 2004 Jan 1;69(1):97-100

Table 1: Contraceptive methods

	Effectiveness (%)		Hormones	Advantages	Disadvantages	Other comments
	Perfect use	Typical use
Tubal ligation	>99.5	>99.5	Nil	Immediate effect	Requires hospital admission and surgery
Vasectomy	99.5	99.5	Nil	Performed under local anaesthetic	Small risk of infection and sperm granuloma	Need semen analysis at 3 months to ensure azoospermia
Mirena® IUD	>99	>99	Progestogen only	Reduces menstrual loss. Cost effective. Suitable for women with contraindications to oestrogen.	Irregular bleeding or spotting may occur in first few months. Some women have progestogenic side effects	Provides endometrial protection for women on MHT.
Kyleena® IUD	>99	>99	Progestogen only	Smaller dose of progestogen than Mirena®. Cost effective. Suitable for women with contraindications to oestrogen		Does not provide endometrial protection for women on MHT. Not suitable for women with heavy bleeding around time of menopause.
Implant	>99	>99	Progestogen only	Cost effective. Suitable for women with contraindications to oestrogen.	20% of women have prolonged or heavy bleeding.
Copper IUD	>99	>99	Nil	Hormone free. Cost effective.	Periods may be heavier and more painful
DMPA injections	>99	96	Progestogen only	Useful for women with heavy menses	Reduces bone density	Not recommended for women > 45
Combined oral contraceptive pill (COCP)	>99	93	Oestrogen and progestogen	Convenience	Not suitable for women with VTE of complex migraines.	Not recommended for women > 50. Consider ceasing by age 45 if cardiovascular risk factors.
Vaginal ring NuvaRing®	>99	93	Oestrogen and progestogen	Works same as the COCP but no tablet taking	Same as for COCP	Same as for COCP
Progestogen only Mini Pill	>99	93	Progestogen only	Suitable for women with contraindications to oestrogen	Must be taken daily within a 3 hour time frame
Diaphragm	86	82	Nil	Hormone free. Prevents STI’s	Risks of urethral irritation, UTI and incorrect placement
Male condom	98	88	Nil	Hormone free. Prevents STI’s Widely available.	Some feel it interferes with sexual pleasure
Female condom	95	79	Nil	Hormone free Prevents STI’s	Difficult to find; purchased online	not commonly used in Australia (? NZ)

Table 2: Emergency contraception

	Hormones	Advantages	Disadvantages	Other comments
Levonorgestrel (LNG- EC)	Progestogen	Readily available at pharmacies without a prescription. Very safe with few side effects	Does not provide ongoing contraception	Ideally take within 72 hours of intercourse
Ulipristal acetate (EllaOne®)	Progesterone receptor modulator		Does not provide ongoing contraception	Can be used for up to 120 hours after intercourse. Don’t use with LNG-EC within the same cycle. Superior efficacy to LNG-EC.
Copper IUD	Nil	Highly effective Contraceptive effect is ongoing	Difficult to access within appropriate time frame

Content Updated July 2022