27 January, 2020

A comment on Climacteric Editor’s Choice "Sexual quality of life in men and women after cancer" by L. R. Schover

Summary

There is a global agreement about the fact that cancers and cancer therapies have a negative impact on the sexual health of men and women with prevalence rates on average of 50-60%. There is also global agreement that patients are very often left alone with their sexual problems and that there is not adequate care. In this review [1], the physical and psychosocial consequences of cancers and cancer treatment on the sexual life of male and female patients are summarized. The barriers and gaps are described. Lack of information and counseling during oncological care, reluctance of patients to bring up sexual issues in a medical environment, lack of training of oncological professionals, lack of time, lack of education material, non-familiarity with the variety of sexual orientations and preferences, focusing on heterosexual penetrative intercourse, etc.. The review [1] describes the short history of initiatives in the US to respond to these barriers and gaps. The National Comprehensive Cancer Network (NCCN) issued guidelines (2019 (https://www.nccn.org/professionals/physician_gls/default.aspx#supportive)), ASCO also issued a guideline in 2017 (https://www.asco.org/research-guidelines/quality-guidelines/guidelines/patient-and-survivor-care#/28976) with some agreement on the basic requirements. The cancer team should initiate discussion about sexuality and provide follow-up visits with the possibility to refer to multidisciplinary treatment.

20 January 2020: 

Summary

The ESTEEM trial (Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence) was published in JAMA earlier this year [1]. This is a randomized controlled trial of women with moderate to severe mixed urinary incontinence (both stress and urge) who underwent mid-urethral sling surgery. One group was given behavioral and pelvic floor muscle therapy for 1 session pre-operatively and five sessions post-operatively. The second group just underwent surgery with no other specific intervention. The primary outcome measure was a change in Urinary Incontinence (UI) symptoms at 12 months as assessed by the Uro-genital Distress Inventory (UDI) score (maximum 300), which is a validated tool for this type of analysis. Four hundred eighty women were randomized across nine sites in the US. In the combined group, the UDI score fell from 178 to 30.7 (mean change - 128 points), and in the surgery only group, the score dropped from 176.8 to 34.5 (mean change -114.7 points). Both groups significantly reduced the UDI score. The difference between the two groups just reached significance (p = 0.04), but this did not meet the pre-specified threshold for clinical importance (35 points). The difference between the two groups was noted primarily in the irritative component of the UDI score, whereas there was little difference in the stress component. Episodes of urge incontinence were reduced in the combined group, and this group was significantly less likely to need additional treatment for lower urinary tract symptoms (8.5% vs. 15.7% OR 0.47 95% CI 0.26-0.85). Adverse events occurred in 10.2% of participants. The authors concluded that amongst women with moderate to severe mixed urinary incontinence combined behavioral and pelvic floor muscle therapy resulted in a reduction in urinary incontinence symptoms, which may not be of clinical importance.

13 January, 2020: 

Summary

A recent study by Chen et al. (1) analyzed a sample of 2,683 postmenopausal women from the Women’s Health Initiative (WHI) cohort, with normal body mass index (BMI; 18.5 to <25 kg/m2), no known cardiovascular disease (CVD), and for whom data was available on body composition, as determined by dual-energy X-ray absorptiometry (DXA). After a median follow-up of 17.9 years, there were 291 cases of CVD (coronary heart disease [CHD], stroke, or the combination of both). After adjusting for confounding factors (i.e., demographics, lifestyle, clinical factors), neither whole-body fat mass nor fat percentage was found to be related to CVD risk. Higher percent trunk fat and leg fat were associated with an increased and decreased risk of CVD, respectively. The association of trunk fat with CVD risk was attenuated but remained significant even after adjusting for waist circumference or waist-to-hip ratio. A combination of higher trunk and lower leg fat was linked to a higher CVD risk. The authors concluded that, in postmenopausal women with normal BMI, both elevated trunk and reduced leg fat increase the risk of CVD.

16 December 2019: 

Summary

The WHI studies (both the clinical and the observational) have provided a wide arrow of information on many aspects of menopause and hormone therapy. A new WHI release, which included a subset of women enrolled in the WHI trials, correlates DNA-derived data with sleep (1). While it is difficult to put into the format of Menopause Live all the details of this study, here are the main features: 1796 European Americans, 1349 Afro Americans, mean age 64. Blood samples from the participants at entry allowed extraction of leucocyte DNA and determining the telomere length (TL). Sleep duration was recorded through a questionnaire, asking women to disclose their normal sleep duration (in round hours) and the degree of sleep disturbance (using the WHI Insomnia Rating Scale). As part of the WHI study protocol, many other demographic, clinical and laboratory variables a ; some were used in the statistical evaluation and adjustments of the current main study data. The bottom-line results can be summarized as follows: mean TL was 214-base-pairs longer in Afro Americans than in European Americans; each 1-year increase in age was associated with 23-base-pair shorter TL, on average; each additional daily hour of sleep beyond 5 hours, approximately, was associated with a 27-base-pair longer TL in the entire sample.

Commentary

A telomere is a nucleoprotein complex found in the extremes of the chromosomes, where its structure is different from the rest of the chromatin since it contains non-coding DNA. The role of the telomeres is to hinder the loss of important DNA from chromosome ends during replication. Short leukocyte TL is associated with increased risks of mortality, cardiovascular disease, diabetes, Alzheimer's disease and probably with cancer as well.

3 December 2019: 

a comment on Climacteric Editor’s Choice 

“Safety of hormone replacement therapy following risk-reducing salpingo-oophorectomy: systematic review of literature and guidelines” by RFM Vermeulen et al.

Summary

Risk-reducing bilateral salpingo-oophorectomy (RRBSO), is the gold standard preventive method to avoid ovarian cancer in women at increased risk. However, by choosing this option, a significant number of women end up with premature iatrogenic surgical menopause with several unwanted health effects. Although hormone (HT) is the only effective strategy to compensate significantly for the hormonal deprivation, there are concerns about the safety of HT in these women with regards to breast cancer (BC) and this is an ongoing challenge for clinicians. Hence, it is important to bridge the gap between risk perception and HT prescription with evidence-based clear advice on HT for women considering RRBSO. The recent publication by Vermeulen et al. is a review of seven articles and 11 National guidelines, which recognized that the short-term use of HT following RRBSO is safe in BRCA1 and BRCA2 mutation carriers [1]. The literature is more reassuring regarding the use of estrogen alone than of combined preparations, however, the use of progestogens cannot be avoided in women with uterus preservation in order to achieve endometrial protection. The evidence for HT safety in premenopausal women without a personal history of BC who undergo RRBSO is scarce. The authors advocate that these subsets of women with prematurely induced menopause need to be counseled for shared decision making on the ideal dose and duration of HT, using the best available information on safety and efficacy.

Commentary

Women carrying a BRCA mutation have an increased risk of developing breast and ovarian cancer [2] In the absence of robust screening tools, prophylactic surgical removal of the adnexa is the current key strategy to reduce the burden of ovarian cancer in BRCA1/2 carriers [3]. The bilateral salpingo-oophorectomy, with or without the additional risk-reducing mastectomy, reduces the risk of ovarian cancer by 80- 96% and breast cancer up to 50%. [4,5] Sixty-five percent of women will opt for RRBSO; women carrying a BRCA 1 mutation will undergo the procedure between 35 and 40 years of age, those with a BRCA1 and BRCA2 mutation, between 40 and 45 years and those with a RAD1C/1D mutation, between 40 and 50 years of age.[6] There is growing evidence from observational studies that RRBSO has a detrimental impact on the quality of life, longevity and on all-cause non-survival endpoints in these women, in particular in those carrying a BRCA1 mutation, who are likely to have surgery earlier than those carrying a BRCA2 mutation.[7]

18 November, 2019: 

a comment on Climacteric Editor's Choice "Benefit-risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John’s wort in breast cancer"

Summary

Breast cancer patients treated with endocrine therapies can suffer severe climacteric vasomotor and psychological symptoms as a consequence of the anti-estrogenic effects; hence, treatment adherence can be compromised. To determine if these symptoms can be treated with specific herbal medications, the authors of the present paper reviewed the benefit-risk profile of a standardized extract of isopropanol Cimicifuga racemosa (iCR) REMIFEMIN®, and a higher dose iCR preparation in a fixed combination with Hypericum perforatum (HP/iCR) REMIFEMIN PLUS®, in women surviving breast cancer, treated or not with tamoxifen (TMX) or aromatase inhibitors. The review is based on a systematic literature search (1997 - April 2018) analyzing clinical studies in breast cancer patients, as well as experimental data on biological effects in breast cancer cells, in animal models of breast cancer, in human breast cancer tissue, and studies on the metabolism of endocrine therapies. The authors concluded that there is a favorable benefit/risk profile of both herbal medicinal products, that could offer a non-hormonal therapeutic option for these women [1].

Commentary

Knowledge of the efficacy and safety of phytopharmaceutical treatment options for climacteric symptoms is much needed, especially for women undergoing endocrine treatment for breast cancer. Ruan and colleagues analyzed data on Remifemin® (iCR) and Remifemim Plus® (HP/iCR), standardized registered phytopharmaceuticals produced in Germany by Schaper & Brümmer GmbH–Co.KG, with certified quality of manufacturing [1]. These specific extracts were already reviewed in 2013, with results distinguishing them from other CR preparations [2]. In 2012, a Cochrane Systematic Review had concluded that there was insufficient evidence to support the use of black cohosh for menopausal symptoms [3]. However, a later review reported a significant efficacy of black cohosh on vasomotor symptoms and on psychological climacteric symptoms [2]; this review was based on 9 clinical studies, of which two were double-blinded placebo-controlled (Remifemin® (n=304 women 12-week duration), and Remifemin Plus® (n=301 and 16-week duration)), another was blinded versus tibolone, and the others were open versus low-dose transdermal estradiol. Ruan and colleagues state this is Oxford Level 1 evidence of efficacy [1].

11 November, 2019: 

Mrs. X is 50 years old and recently postmenopausal, having had her last menstrual period a year ago. She laments climacteric symptoms and asks about the risks and benefits of menopausal hormone therapy (MHT). During the consultation, she refers that she has been affected by Systemic Lupus Erythematosus (SLE) since the age of 38 years. She has no other health problem. Mrs. X experienced a miscarriage at the age of 24 years and then had a live birth at the age of 25. The pregnancy was uneventful. In her family, there is no history of breast or ovarian cancer; her father has had type 2 diabetes since the age of 6O, with some vascular complications, and her mother suffers from hypertension and hypercholesterolemia. Her first SLE flare occurred at the age of 37 years and presented with fatigue, joint pains, hair loss and skin lesions especially on the face and the upper thorax. She first consulted her general practitioner who prescribed some tests and suspected SLE. She was sent to a specialist who confirmed the diagnosis based on clinical and biological criteria; arthritis, skin lesions, alopecia, fatigue and an increase in c-reactive protein, discrete leukopenia, a decrease in total complement levels and positive anti-DNA and anti-smooth muscle antibodies. She underwent a series of tests that excluded kidney, brain, heart or lung involvement and antiphospholipid antibodies. It was concluded therefore that Mrs. X had cutaneous articular SLE. She took hydroxychloroquine for 10 years but had to stop it. She has had several flares over the years with increasing involvement of joints but of no other sites. She has taken corticosteroids 3 times for short periods. She is currently without treatment and her last flare occurred more than 5 years ago.

How will we answer her question on the benefits and risks of MHT? [for details see reference 1]

SLE is an autoimmune disease that can be worsened by estrogens. Before puberty and after menopause, the female: male ratio is about 2-3:1, whereas, during childbearing age, this ratio reaches 10-13:1. Genetic factors linked to chromosome X are also associated with the prevalence in women. In 30% of the cases, SLE antiphospholipid antibodies or lupus anticoagulant (APL) may be present. SLE is associated with an increase in cardiovascular disease and osteoporosis at a young age. The frequency of cardiovascular events is proportional to the duration of SLE and associated with renal involvement.

28 October, 2019: 

I’ve been reading...

The Broken Eye, by Brent Weeks, described as ' epic fantasy'; I have been reading the series. I usually start during my summer holidays, which unfortunately end too soon, and then I tend to finish the books when I am in the midst of plane travel!

I’ve been researching...

Entertainment options for our international visitors who are coming to the IMS Congress in Melbourne in late April 2020. I am hoping that a large fluffy koala or kangaroo may be involved somehow.....

My team...

I am a member of a few teams! These are The Australasian Menopause Society, The Women's Health Research Program at Monash University, and Jean Hailes for Women's Health. I am incredibly lucky to work with people who are passionate about women's health and education and work hard to get evidence-based health information out to both the community and health practitioners.

An anecdote...

If you come to Melbourne to the IMS Congress https://www.imsmelbourne2020.com/ next year by plane you may see kangaroos greeting you from within the paddocks (fields) not far from the airport. There are quite a number of them and, apart from being there to welcome you, they are sometimes found hopping around the airport car-park. This is not supposed to happen but never fails to make it onto the nightly TV news bulletin. If you don't see one when you travel from Melbourne airport next year I am still working on the large variety discussed in question 2, as part of the entertainment program!

An interesting case...

One of my patients today described being exceptionally tired some months ago in the setting of having a several months old infant, who was fully breastfed. She thought the lethargy was out of context as she was otherwise managing everything quite well. She then presented to her doctor recently as she felt something moving in her abdomen. Yes, she is having another baby and didn't quite notice until she had reached the second trimester.

I’m worried about...

Being in a world in which it seems that people no longer try to look out for each other.

I’ve been thinking...

About the IMS Congress in Melbourne https://www.imsmelbourne2020.com/ next year, of course! I can't wait. It's going to be amazing. (Don't forget!)

21 October, 2019:  

Summary

Recent publications have shown that estrogens and vitamin D have a synergistic effect, not only on bone health but also on insulin resistance and metabolic syndrome [1,2,3]. Underlying mechanisms for these associations are not clear and several possible explanations have been suggested. Vitamin D may have an insulinotropic effect by increasing intracellular calcium concentration in pancreatic beta-cells. Vitamin D may also act as an inhibitor of sterol regulatory element-binding proteins activation, thus controlling lipid homeostasis. Finally, vitamin D levels affect the nitric oxide signaling pathway in the arterial muscle, leading to an abnormal vasodilator activity [2,4,5]. Clinical trials have also reported that vitamin D supplementation may reduce visceral adipose tissue in overweight or obese adults [6].

Hui Huang and his group carried out an observational and cross-sectional study [7], evaluating 616 postmenopausal women (aged 49-86 y) from southern China, who were not taking estrogen and vitamin D or calcium supplements, to assess the role of vitamin D levels in relation to metabolic syndrome and estradiol (E2) levels. The participants were classified into two groups based on vitamin D levels (25(OH)D < or ≥ 50 nmol/L). In participants with optimal serum levels of vitamin D (≥ 50 nmol/L), there was no significant correlation between estradiol and metabolic syndrome, after adjusting for confounding factors. In the other group of women,  the adjusted odds ratio (OR) for metabolic syndrome significantly increased with decreasing serum 25(OH)D (OR 2.19, 95% CI, 1.19-4.01 for comparisons of vitamin D deficient versus sufficient; P for trend 0.009). This association remained unchanged after further adjusting for estrogen levels. Postmenopausal women who were vitamin D deficient presented a negative correlation between estradiol levels and metabolic syndrome risk (OR 3.49, 95% CI, 1.45-8.05 for the lowest versus the highest tertile; P for trend 0.006). The present study observed that vitamin D deficiency is an independent risk factor for metabolic syndrome in postmenopausal women. Moreover, the authors observed an inverse association between estradiol levels and metabolic syndrome, which tends to be stronger in participants with vitamin D deficiency than in those with adequate circulating levels of the vitamin.

Commentary

The risk of cardiovascular disease increases after menopause and may be related to the substantial metabolic changes that take place as women transition from premenopause to postmenopause. The prevalence of metabolic syndrome increases with age. Many cross-sectional studies have shown an increased risk of metabolic syndrome in postmenopausal women, which varies from 32.6% to 41.5% [8,9]. In medical literature, observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes [10]. However, the results of intervention studies have been inconsistent [11, 12]. This observational study emphasizes the possible synergistic role of vitamin D and estradiol deficiency in causing metabolic syndrome in postmenopausal women. If these results are confirmed in randomized controlled trials, correction of inappropriate levels of vitamin D may become widespread in clinical practice, not only to preserve bone but reduce the manifestations of the metabolic syndrome and its consequences.

3 October 2019: 

IMS Collaboration with the 11th International Congress on Menopause and Gynecological Endocrinology
Beijing, China, September 6th - 8th 2019

IMS current Board Member Professor Xiangyan Ruan and past Board Member Professor Alfred O.Mueck recently chaired the "11th International Congress on Menopause and Gynecological Endocrinology" in Beijing from September 6th - 8th, 2019. The congress was sponsored by the Beijing Obstetrics and Gynecology Hospital, Capital Medical University in collaboration with the following societies: International Menopause Society (IMS), International Society of Gynecological Endocrinology (ISGE), Chinese Society of Gynecological Endocrinology affiliated to ISGE (CSGE), European Menopause and Andropause Society (EMAS), European Society of Gynecology (ESG), International Academy of Human Reproduction, Chinese-German Society of Obstetrics and Gynecology, German Menopause Society, German Society of Gynecology and Reproductive Medicine, German Society of Endoscopy, German Society of Endometriosis, European Society of Endometriosis, Osteoporosis Society of China Association of Gerontology and Geriatrics (OSCAGG) and Beijing Obstetrics and Gynecology Society of Endocrinology.

Twenty-three speakers from all over the world attended this congress with an audience of 500 participants. Most of the members of the audience were experts in the field of Gynecological Endocrinology in large hospitals coming from the Beijing Region and from all over China. The event was considered the highest-ranking international congress in China to date in this field of medicine. Eight international speakers are presently visiting professors at the Beijing Obstetrics and Gynecology Hospital, Capital Medical University, China. During the Congress, there were outstanding lectures from the Chinese speakers on special diseases like PCOS, POI, endometriosis and hyperprolactinemia, bleeding problems (AUB), endometrial abnormalities, sexual disorders, pregnancy and offspring health, ART, diagnosis, and treatment of fertility problems. There were several lectures from Chinese and international experts on fertility preservation, especially ovarian cryopreservation, a technique that was implemented in China for the first time by the Beijing Obstetrics and Gynecology Hospital. 

The following lectures were presented by current members of the IMS:

• "IMS Guidelines for Menopausal H Professor Ruan’s team for their ongoing effort in translating abstracts into Chinese for CLIMACTERIC. This has encouraged submissions on behalf of Chinese researchers to the journal such that, at present 21% of the papers are published by Chinese scholars.

• ormone Therapy" by current IMS President Professor Susan Davis  

• "Treatment Options for Vaginal Atrophy" by IMS Past President Professor Andrea Riccardo Genazzani

• "POI: Cancer Survivorship - Mitigating (reducing) the Consequences of Iatrogenic POI" by IMS General Secretary and Past Editor-in-Chief of CLIMACTERIC, Professor Nick Panay

• "The different methods of fertility protection in cancer patients" by Professor Sven Skouby  

• "IMS IMPART", a presentation of the IMS internet-based educational program for students and doctors, by Professor Rod Baber, Immediate Past President of IMS and Editor in Chief of the SCI-journal CLIMACTERIC 

• "Prevention and Treatment of Osteoporosis in Peri-and Postmenopausal women" and "Tibolone as Special Option for Treatment of Postmenopausal Patients" by past IMS Board Member and current ISGE Treasurer, Professor Martin Birkhaeuser 

• "Management of PCOS" and "The first Chinese POI database cooperated with the Royal College and prevention and treatment of iatrogenic POI: the first Chinese guideline on ovarian tissue cryopreservation and transplantation"  by Professor Xiangyan Ruan 

• "Breast cancer and MHT", a presentation discussing the carcinogenic mechanism in breast cancer development based on experimental data and clinical data, including that of the very recent publication in The Lancet, by Professor Alfred O. Mueck.

• A number of other excellent lectures were delivered, including that of Professor Thomas Rabe on "Amenorrhoea - etiology, diagnosis, and therapy". Professor Rabe is well known and appreciated in China because his ancestry; his grandfather, John Rabe, saved thousands of Chinese during the Second World War from the Japanese Nanjing Massacre.

All lectures were well received by enthusiastic audiences.