草莓视频

28 June, 2019

Who are the women that live longer?

Summary

A new study from the Netherlands attempted to find markers that may predict higher longevity in women [1]. A subgroup of the Netherlands Cohort Study (NLCS) consisted of those who were born in 1916-1917 and were followed until death or until reaching age 90 (in the years 2006-2007). Out of 2697 eligible women with complete data, 928 lived to be 90 and 1769 died at earlier ages. Lifestyle, dietary habits, reproductive and medical history, and cancer risk factors were collected when women were around age 70, using a self-administered 11-page questionnaire. Mortality was recorded based on a linkage with central national registries. The results were rather disappointing, as very few parameters were found to significantly correlate with longevity: age at first childbirth, and ever-use of HRT in women with an early menopause (< 50 years) were associated with the likelihood of reaching the age of 90 years. Many other variables, generally thought to be relevant to longevity, failed to show a linkage (i.e., age at menarche or at menopause, menstruation lifespan, history of childbirth).

Commentary

Despite the universal wish to better understand the reasons why women live longer than men, and what might in general be the reasons for extreme longevity, this Dutch study did not provide definite answers. Interestingly for menopause specialists, ever-use of HRT in women entering menopause before age 50 did influence longevity.

Personally, I was not surprised to see the above results, since the issue of longevity is certainly very complex, involving genetic and medical, dietary, socio-economical, environmental and other factors. Just one example that might affect the outcomes of this particular cohort: the participating women were born during World War 1 and lived several years within their occupied country during World War 2. I would imagine that this might have had an impact on future health and disease, on physical and emotional parameters and on reproductive factors. Also, and not taking a view as an expert epidemiologist or a statistician, the fact that the cohort was rather small, and the variables tested were so many, makes it a-priori very difficult to reach significance for any potential association.

10 June 2019: 

Summary

In 2010 Bolland et al. published a small meta-analysis suggesting increased cardiovascular events among women randomized to calcium.[1] As the initial controversy escalated, driven by fears spread through the popular press, the New Zealand group obtained data from the WHI and published an analysis that they interpreted to show that, in women who were not taking calcium and vitamin D supplements when they were randomized, there were modest increases in cardiovascular events in those assigned to calcium and vitamin D compared to those randomized to placebo.[2] The WHI investigators published a paper attempting to replicate those findings using the same dataset; those analyses -- using exposure at the time of WHI enrollment -- demonstrated no such hazards.[3,4] Now this group comes with a strategy similar to their initial run at calcium, combining a large number of mostly small studies into a meta-analysis. [5] They included 81 studies evaluating a range of vitamin D doses that addressed at least one of 3 outcomes: fractures, falls or bone mineral density (n of studies = 41, 37 and 41, respectively). Over two-thirds were of less than one year鈥檚 duration. The relative risk for total fracture was 1.0; 95% CI 0.93-1.07, for hip fracture 1.11; 0.97-1.26 and for falls 0.97; 0.93-1.02. Overall, the authors state 鈥淚n meta-analysis of 81 randomised controlled trials, vitamin D supplementation did not affect incident fractures or falls, and did not have consistent clinically relevant effects on bone mineral density.鈥� They write that their results show 鈥渢hat there is reliable evidence that vitamin D supplementation does not have meaningful clinical benefits.鈥�

3 June 2019: 

Summary

In 2010 Bolland et al. published a small meta-analysis suggesting increased cardiovascular events among women randomized to calcium.[1] As the initial controversy escalated, driven by fears spread through the popular press, the New Zealand group obtained data from the WHI and published an analysis that they interpreted to show that, in women who were not taking calcium and vitamin D supplements when they were randomized, there were modest increases in cardiovascular events in those assigned to calcium and vitamin D compared to those randomized to placebo.[2] The WHI investigators published a paper attempting to replicate those findings using the same dataset; those analyses demonstrated no such hazards.[3,4] Now this group comes with a strategy similar to their initial run at calcium, combining a large number of mostly small studies into a meta-analysis. [5] They included 81 studies evaluating a range of vitamin D doses that addressed at least one of 3 outcomes: fractures, falls or bone mineral density (n of studies = 41, 37 and 41, respectively). Over two-thirds were of less than one year鈥檚 duration. The relative risk for total fracture was 1.0; 95% CI 0.93-1.07, for hip fracture 1.11; 0.97-1.26 and for falls 0.97; 0.93-1.02. Overall, the authors state 鈥淚n meta-analysis of 81 randomised controlled trials, vitamin D supplementation did not affect incident fractures or falls, and did not have consistent clinically relevant effects on bone mineral density.鈥� They write that their results show 鈥渢hat there is reliable evidence that vitamin D supplementation does not have meaningful clinical benefits.鈥�

27 May, 2019:

Summary

This publication from the WHI data evaluates the relationship of vasomotor symptoms (VMS) to breast cancer incidence and mortality [1]. It was observed that there was a statistically significant increase of breast cancer incidence in those women with persistent vasomotor symptoms compared to those without vasomotor symptoms HR 1.13 CI (1.02-1.27) yet no statistically significant impact on survival was noted (HR 1.33 CI 0.88-2.02). Vasomotor symptoms were assessed via a self-administered baseline questionnaire in 40 centres across the US to 161,808 women, ages 50-79, between 1993 and 1998. After applying exclusion criteria, such as use of hormone therapy, 25,499 postmenopausal women remained in the analytic sample. Duration of symptoms was determined by VMS history before baseline enrolment. 鈥淣o vasomotor symptoms鈥� was defined as 鈥渘ever experienced and none experienced over the last 4 weeks. 鈥� Persistent VMS鈥� included moderate or severe symptoms ever or within the 4 weeks before WHI entry. Breast cancers that developed during follow-up for 8.5 years were verified by review of medical records. Cause of death was ascertained via the National Death Index. Breast cancer incidence, mortality and the association with VMS were calculated using time dependent Cox regression analyses adjusted by breast cancer risk factors. 1,399 breast cancers occurred over 17.9 years of follow-up. 9,715 women with persistent VMS for 10+ years had a hazard ratio of 1.13 ( CI 1.02-1.27) for developing breast cancer compared to 15,784 women without VMS. ER - cancers, both regional and metastatic, occurred more frequently in patients with persistent symptoms. Although deaths from breast cancer were higher in the women with persistent VMS, this result was not statistically significant (HR 1.33 (CI 0.88-2.02)) [1].

22 May 2019: 

I鈥檝e been reading鈥�

鈥�21 lectures for the XXI Century鈥�, by Yuval Noah Harari. This is an interesting book which comments about the facts and challenges that new generations have to face. This book presents different points of view regarding the loss of jobs due to new artificial intelligence and other topics, such as immigration and the impact of global warming.

I鈥檝e been researching鈥�

into the development of new drugs for Osteoporosis and for type 2 Diabetes in phase III trials.

My team...

is working on continuing medical education in Endocrinology, Menopause and Osteoporosis. We have optimized National Guidelines on Menopause and Osteoporosis Management. We are now working on the National Recommendations for Calcium and Vitamin D therapy and on the validation of the FRAX score In coordination with the Minister of Health of Costa Rica.

An anecdote鈥�

as the President of FLASCYM (Latin American Federation of Menopause Societies), I organized the IX FLASCYM Congress in Costa Rica, which took place from March 26th to 29th, 2019. After many months of effort we hosted 390 participants and got the collaboration of 47 speakers. We had a Precongress Practitioner Refresher Training course in Menopausal Medecine (IMPART), with 180 attendees, thanks to the great contribution of Professor Susan Davis, IMS President, and Dr. Nick Panay, Dr Camilo Rueda and myself as members of the IMS Board. We received excellent comments about the IMPART Program to the extent that various organizations in Latin America have expressed their interested in including a Precongress IMPART course as part of their local academic events.

An interesting case...

is that last week I received a 73-year old lady at my office, which had been taking oral MHT since her 50s. She had many questions about a mild plasma glucose increase, spongiform thyroid nodule with a biopsy indication, and oral/ transdemal MHT. She referred that each time that she had tried to stop MHT, sleep became disturbed and multiple daily episodes of intense vasomotor symptoms recurred. She had an excellent densitometry report, with normal t-score at her spine and mild low hip bone density. I just proposed some lifestyle modifications, such as more excercise and a reduction in carbohydrate and fat intake. Moreover I switched her MHT from oral to transdermal, recommended against the thyroid biopsy as it was not indicated and suggested a check-up after four months. This case makes me think about the need we have to support clinical care of older MHT users, based on scientific evidence.

I鈥檓 worried about...

the overpopulation of doctors in my country who have no work, after long years of study. This means that in order to survive economically, they leave aside their continuous medical update that is so important in our profession. I鈥檝e been thinking... what the best way is to transfer knowledge in continuous medical education programs. We should probably prefer active clinical case discussion sessions to theoretical lectures.

In my spare time鈥�

I love to cook and experiment with new recipes on Sundays during family lunch. I also like to organize family field trips to places far away from San Jos茅, capital of Costa Rica, to admire nature; we like to get up early in the morning to go bird-watching.

13 May 2019

Commentary on 鈥淚s there a role for mindfulness-based interventions (here defined as MBCT and MBSR) in facilitating optimal psychological adjustment in the menopause?鈥� by Wendy Molefi-Youri.

Summary

As life expectancy increases worldwide, a growing number of menopausal women are facing psychological and physical symptoms. This calls for individualized patient care in view of unique bio-psycho-sociocultural and environmental factors and variation in ethnicity and access to care. Furthermore, the efficacy of various therapeutic interventions needs to be considered in view of the long-term adverse effects. Recently published, the overview by Wendy Molefi-Youri summarizes the literature of efficacy for mindfulness-based interventions (MBI). [1] The author explored the potential aetiology of distress during menopausal transition and paid attention to the mechanism by which mindfulness training facilitates optimal psychological adjustment during menopause and beyond. Although current available evidence is promising, considering these interventions in our clinical practice, the author raised reasonable practical questions: Would menopausal women be interested in engaging with these interventions? Are there any potential barriers? Would it be necessary to adapt the existing MBIs in order to meet the needs of this population?

Commentary

Women suffer from a cluster of symptoms during menopausal transition which adversely affect their overall quality of life. They often seek attention for non-hormonal treatment due to medications risks or personal preference or contraindications to menopausal hormone therapy (MHT). There is a need for psychological and behavioural interventions which can potentially mediate the reaction to menopause-related symptoms and increase resilience and coping skills. Many organizations have emphasized the need for a comprehensive multi-faceted approach to women鈥檚 needs which includes holistic interventions. [2,3,4,5]. Studies have suggested that reducing negative emotion such as anxiety, stress and depression, may help women make a smooth menopausal transition. Non-hormonal strategies for vasomotor symptoms include Mindfulness-based Stress Reduction (MBSR) [6,7]. Mindfulness-based training, i.e. a psychological intervention that targets perception and acceptance, may be a non-pharmaceutical alternative. Mindfulness-based cognitive therapy can also complement existing treatments for menopausal symptoms by teaching women self-compassion and thereby reducing distress. MBSR therapies consist of sitting and walking meditation, gentle yoga poses, and body awareness exercises such as body scan. The technique helps women pay attention to the present moment in a non-judgmental and accepting way. The resulting calming effect helps to relieve stress. Studies have indicated that MBIs are effective in mitigating menopausal symptoms. Although better understanding of the mechanism is needed, these interventions primarily affect the psychological aspects of the symptoms, by reducing the reactivity to stimuli and dampening the perceived severity of symptoms. Preliminary research has suggested a significant reduction in cortisol levels, which corelate with the stress response.[8]

22 April 2019: 

I鈥檝e been reading鈥�

The Gathering Storm by Winston Churchill; Churchill鈥檚 perspective on the events leading up to and into the second world war.

I鈥檝e been researching鈥�

pharmacologic approaches to relieving menopausal symptoms.

An anecdote鈥�

you may wonder what governments and camels have in common. According to an old Saudi Arabian proverb, "if the camel once gets his nose in a tent, his body will soon follow鈥�.

I鈥檓 worried about鈥�

the illusion that government funded studies are not associated with conflicts of interest.

I鈥檝e been thinking鈥�

about approaches to treating conflicts of interest associated with journal publications equally regardless of the funding source of the research.

In my spare time鈥�

I enjoy traveling to get together with friends around the world.

15 April 2019: 

Summary

Ablation of estrogen receptor alpha (ER伪) in the medial basal hypothalamus results in a robust bone phenotype only in female mice that ends in exceptionally strong trabecular and cortical bones, the density of which surpasses that reported in other mouse models.

Commentary

The role of estrogens in regulating reproduction in females is known, but the role it plays in the brain remains uncharacterized. Estrogen works jointly with vitamin D and calcium to preserve the regulation of bone turnover. After menopause, as the levels of estrogen in the body decline, the rate at which bones are rebuilt increases and the skeleton begins to lose more mineral content than it produces. Central estrogen signaling coordinates energy expenditure, reproduction, and, in concert with peripheral estrogen, affects skeletal homeostasis in females. In this study, Herber and collegues ablated estrogen receptor alpha (ER伪) in the medial basal hypothalamus and this action caused the mice to gain weight and become less active. To the authors鈥� surprise, the weight gain was due to an 800 percent increase in bone mass. Aside from an increased density, the bones of the animals also had an increase in strength. This increased strength and density did not falter as the mice aged,  leading to a robust bone phenotype only in female mice that resulted in exceptionally strong trabecular and cortical bones, the density of which surpassed that of other mouse models [1]. Stereotaxic-guided deletion of ER伪 in the arcuate nucleus increases bone mass in intact and ovariectomized females, underlining the central role of estrogen signaling in this sex-dependent bone phenotype. Loss of ER伪 in kisspeptin (Kiss1)-expressing cells is sufficient to recapitulate the bone phenotype, identifying Kiss1 neurons as a critical node in this strong neuroskeletal circuit. The precise neuronal or humoral signals that promote the high mass bone phenotype in females remain to be determined. However, this phenotype is independent of changes in leptin or estradiol and is not directly influenced by ER伪 neurons in the ventro-medial hypothalamus (VMH). These findings differ from prior reports linking leptin deficiency to high trabecular bone mass [2] via a circuit involving suppression of serotonergic signaling in the VMH [3] or direct effects of leptin on bone [4]. In conclusion, this study demonstrated that estrogen plays a different role in the blood than it does in the brain. In the blood, estrogen contributes to bone stability, while in the brain, estrogen seems to limit bone formation. This newly-identified female brain-to-bone pathway exists as a homeostatic regulator diverting calcium and energy stores from bone building when energetic demands are high. This study reveals a new target for treatment of osteoporosis.

8 April 2019: 

Commentary on "Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases" by Vinogradova Y, et al

Summary

It is well known that postmenopausal estrogen or hormone therapy improve vasomotor symptoms, vulvovaginal atrophy/genitourinary syndrome of menopause, prevent osteoporotic bone loss, and even enhance sexual function. However, since the publication of the initial clinical trial results of the Women鈥檚 Health Initiative E+P trial in 2002, use of both estrogen and hormone therapy has decreased despite these benefits. This phenomenon occurred largely due to a shift in focus from the benefits of hormone therapy to the risks of these treatments. Paramount among these risks are the potential for estrogen with or without progestogen to increase deep vein thrombosis and thromboembolism (VTE). While randomized clinical trial information comparing oral vs transdermal or non-oral regimens is lacking, observational studies like this one, demonstrate a reduced risk for DVT and PE with transdermal or non-oral treatments [1]. Risks with such non-oral approaches are comparable to non-users of estrogen therapy even in women with prior thrombotic event histories and obesity, independent risks for thrombosis and thromboembolism [2, 3 for review]. This retrospective analysis by Vinogradova and colleagues consisted of approximately 80,000 women with VTEs compared with about 390,000 non-VTE controls from the QResearch and CPRD databases. The authors found no added risk for VTE associated with estradiol patches, gels, or subcutaneous formulations (adjusted odds ratio: 0.93, 95% CI 0.87-1.01). In contrast, oral estrogen therapy was associated with a significantly increased risk for VTE (adjusted OR 1.58, 95% CI 1.52-1.64). This increased risk remained significant for both estrogen oral preparations (aOR 1.40, 95% CI 1.32-1.48), as well as estrogen+progestogen oral combinations (aOR 1.73, 95% CI 1.65-1.81). Other database reviews document similar findings [4] Further, Vinogradova and colleagues found the risks of VTE with oral conjugated equine estrogens(CEE) or combined formulas of CEE and a progestogen were higher than oral estradiol therapies (aOR 0.85, 95% CI 0.76-0.95; aOR 0.83, 95% CI 0.76-0.91, respectively) and nearly double the VTE risk of women non-users (aOR 2.10, 95% CI 1.92-2.31). Taken together these findings support prior studies documenting the higher procoagulant and thrombotic risks of CEE compared with oral estradiol [5]. Estradiol combined with dydrogesterone, a formulation not available in the US, showed a slightly elevated VTE risk compared to non-users, but the lowest of the combined oral formulations (aOR 1.18, 95% CI 0.98-1.42).

Commentary

In this study, more than half of the women with VTEs were 鈮�65 years of age, and were more likely to have additional comorbidities (cancer, heart disease) versus controls (56% vs 36%). Women with VTE also were more likely than controls to have recent medical problems (27% vs 12%), such as respiratory or urinary tract infections, hip fractures, or surgery with or without hospital admission, or hospital admission for other reasons. These events may have added immobilization to their inherent risks.

25 March 2019: 

Summary

Ovarian cryopreservation and retransplantation for fertility protection is well established in Europe, but not in China or other Asian countries. Four recent publications [1-4] stress that this technique is no longer experimental and should be regarded as a valid ART treatment option especially for some cancer types. However, this technique is not only performed to restore fertility but also to restore ovarian function after surgery, radiotherapy and chemotherapy. China's first official "International Center of Fertility Protection Specialized in Ovarian Tissue Cryopreservation and Transplantation" was established in 2012 within the Beijing Obstetrics and Gynecology Hospital, Capital Medical University, with the help of European experts. In 2016 the first retransplantation of cryopreserved ovarian tissue was performed, and has recently been published as a "case report" [5]. The cryopreservation and transplantation was performed to preserve ovarian function in a patient with squamous cell cervical carcinoma I b1 after surgery. The 35-year-old nulliparous patient came in June 2015 for consultation. During cervical cancer surgery half of her left ovary was removed and transferred to the cryobank. Ovarian cortical strips were frozen using a standardized slow-freezing process and stored in liquid nitrogen. Following 19 cycles of radiotherapy and 3 cycles of chemotherapy, between August 2015 and October 2015, severe menopausal symptoms appeared (estradiol (E2) about 30 pg/ml, FSH > 100 IU/l); these were treated with E2 patches 50碌g/day until August 2016 (E2 about 90 pg/ml, FSH about 50 IU/l). After oncologists confirmed a disease-free condition, the cryopreserved-thawed ovarian tissue retransplantation was performed in September 2016. Thawing of the cortical strips was performed using a standardized protocol and four ovarian tissue fragments were transplantated into a peritoneal pocket in the area of the right peritoneal ovarian fossa. Restoration of ovarian endocrine function was shown in the third month after transplantation, accompanied by a significant reduction in Kupperman score from 37 before transplantation to 5 in the first month after transplantation. The score subsequently remained low and stable.

Commentary

Cryopreserved-thawed ovarian tissue is mainly transplanted orthotopically (i.e. into the peritoneum, into or onto the ovary) [6]. However, in some cases retransplantation is also performed in heterotopic sites, and one pregnancy has been reported worldwide [7]. In our case, the tissue fragments were retransplanted into a peritoneal pocket lateral to the right ovary where the blood supply was proved to be rich. The same approach has been used in most cases of retransplantation in 16 European centres, and has resulted in high success rates and may be an alternative to transplantation into the ovary [8]. The first signs of ovarian activity usually occur after 3 months based on the time of follicular growth, and most patients recuperate ovulatory cycles within 4-9 months after retransplantation [8]. This case may be  very "normal" for other countries, especially in Europe, where ovarian tissue preservation was introduced years ago but, for China, this first report of successful retransplantation represents a milestone in the field of fertility preservation, although until now no live birth has been reported. Worldwide this technique has lead to more than 130 live births were reported until June 2017, and restoration of ovarian activity in over 95% of cases [2]. No frozen-thawed ovarian tissue retransplantation has been previously reported in China, and, to our knowledge, the center in the Beijing OB/GYN Hospital is still the only one to have performed this technique, although other large hospitals in China have been showing a growing interest in establishing a cryobank and performing ovarian preservation and retransplantation. This large interest finds its expression in the "First Chinese Guideline of Ovarian Tissue Cryopreservation and Transplantation" [9]. With regards to the medical content, the consensus is very similar to Western guidelines but with a focus on practical issues joining gynecologists, embryologists, oncologists, pediatricians, breast oncologists, hematologists and experts in Traditional Chinese Medicine (TCM). The guideline includes: selection criteria, evaluation and indications, standard operating procedures of ovarian tissue removal, transportation, preparation, freezing and thawing, approaches to ovarian tissue transplantation and follow-up, practical recommendations for ovarian tissue cryopreservation and transplantation including recommendations of the diseases for which this method could be applied, and treatment of menopausal symptoms during the time between cryopreservation and retransplantation. In our center, currently, the ovarian tissue of more than 200 patients has been cryopreserved and six other patients have undergone successful retransplantation. To understand the importance of China's first center the special situation of fertility protection in China must be considered. Until 2016 China (with some exceptions in the countryside) was officially ruled under the "One-Child-Policy", without much support to the introduction of new techniques in the field of fertility protection.