NAMS video series 2019: Understanding the etiology and mechanism of vasomotor symptoms

The North American Menopause Society (NAMS) regularly posts comprehensive videos for clinicians about important midlife health topics. All interviews in the series are hosted by NAMS Board of Trustees Member and Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also a medical consultant for CTV News.

In this first video of 2019, Dr. Rebecca Thurston, Director of the Women’s Biobehavioral Health Laboratory and Professor of Psychiatry, Psychology, Epidemiology, and Clinical and Translational Science at the University of Pittsburgh throws some light on the why and how about vasomotor symptoms (VMS).

The natural history of vasomotor symptoms is still evolving. It is estimated that about 75% of women experiencing menopause will have hot flashes. A substantial number of women seen in everyday gynecological practice or specialty menopause clinic report VMS well past the age of 60 and some well into the 80s.

Hot flashes considerably reduce the quality of life and hamper the day to day activities. Prevalence of VMS is generally associated with increased risk of CVD due to endothelial dysfunction. Hence, women with VMS could be screened for CVD risk factor and offered lifestyle modifications and frequent screening for early diagnosis and prevention.

Ob/Gyn Updated Facebook page

Menopausal transition period is a "critical window" for cardiovascular prevention in women

A healthy lifestyle during the perimenopausal and menopausal years reduces the risk of cardiovascular events in later life report the result of a prospective, cohort study published in in the December 4 issue the Journal of the American Heart Association.

The study is a secondary analysis of data from the ongoing, multicentric, multiethnic, prospective Study of Women's Health Across the Nation (SWAN) initiated in 1996 to know more about transition across menopause.  The researchers looked at data from 1143 women to create a composite 10-year average Healthy Lifestyle Score (HLS) involving smoking, diet quality, and physical activity. All three are modifiable behavioral risk factors for CVD and earlier studies have shown an inverse association between healthy lifestyle and various CV outcomes.

The study participants were followed for an average of 15 years with the last follow-up in the year 2015-2016. Carotid ultrasound scans were performed after 14 years to measure the markers of subclinical atherosclerosis which include common carotid artery intima‐media thickness (CCA‐IMT), adventitial diameter (CCA‐AD), and carotid plaque.

Information about the diet was collected at baseline, visit 5, and visit 9 using a modified version of the Block Food Frequency Questionnaire (FFQ) and the amount was quantified using the Alternate Healthy Eating Index (AHEI).

To assess whether the recommended physical activity (≥150 minutes/week of moderate-intensity physical activity) is met or not, the participants were asked to fill the sports and exercise questions on the Kaiser Physical Activity Survey.

Data on smoking were collected using the standardized questions from the American Thoracic Association.

The HLS was calculated based on the sum of individual scores on all the three parameters at baseline, visit 5 and visit 9 and averaged to get the final score. Other covariates included in the study at baseline were age, race/ethnicity, education, financial status, marital status, depression, self-reported health status, and menopausal status.

Physiological risk factors, including BMI, high blood pressure, impaired fasting glucose, serum triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, use of antilipidemic medications, and use of antihypertensive medications were adjusted in a separate model.

The association between the individual component of HLS and the three markers of subclinical atherosclerosis were also looked at.

At 10 years follow-up, average HLS was found to be inversely and statistically significantly associated with CCA-IMT and CCA-AD — an association that persisted, even after "extensive" adjustment for confounders (P = .0031) and physiological risk factors (P < .001 for both CCA-IMT and CCA-AD).

Compared with participants with the lowest range of HLS, those with highest HLS had a 0.024 mm smaller CCA-IMT and a 0.16 mm smaller CCA-AD.

After adjusting for various physiological risk factors, the researchers did not find a statistically significant association between carotid plaque and average HLS.

Analyzing individual component of HLS, smoking conferred the highest risk for a CV event and those who never smoked had a 0.047 mm smaller CCA-IMT, a 0.24 mm smaller CCA-AD, and 49% lower odds of having a higher carotid plaque index.

The investigators message for the physicians “the menopausal transition represents a crucial, yet understudied, window of increased cardiovascular risk in women. For the prevention of future cardiovascular disease among women undergoing the menopausal transition, the physician should focus on modifiable health behaviors including smoking, diet, and physical activity."

Full text 

Ob/Gyn Updated Facebook page

FDA approves first ever bioidentical hormone combo for treatment of menopausal symptoms

The U.S. Food and Drug Administration (FDA) approved TherapeuticsMD’s oral hormone combo, BIJUVA™ (estradiol and progesterone) for relief from menopause symptoms such as mild to moderate hot flashes, sleep disturbances, and night sweats.

Bijuva is the first and only FDA-approved bio-identical* hormone therapy combination of estradiol and progesterone in a single, oral capsule available for treatment of distressing hot flashes or flushes in menopausal women with a uterus.

Brian Bernick, Co-Founder and Director of TherapeuticsMD said in a press release, “The approval of BIJUVA represents an important and new opportunity for menopausal women suffering from moderate to severe vasomotor symptoms. Menopausal women and their health care providers have been seeking bio-identical combination therapies for many years without an FDA-approved option.”

This is also an important milestone for TherapeuticsMD raking its third approval from FDA this year following Imvexxy, a bioidentical estradiol vaginal insert, and Annovera, a hormonal birth control ring.

The approval is based on results of a large 12 months, well-controlled, multicenter, randomized phase III Replenish clinical trial that has demonstrated both safety and efficacy of the drug in the treatment of moderate to severe hot flashes due to menopause. The study results were published July 2018 in the journal Obstetrics & Gynecology.

The primary efficacy end-point studied was a change in frequency and severity of hot flashes from baseline at weeks 4 and 12 weeks as compared to placebo in the vasomotor symptoms substudy group. Secondary endpoints were responder analyses and menopause-specific quality of life (MENQOL) questionnaire.

The primary safety endpoint of endometrial hyperplasia was evaluated in the entire study population at the end of the study period of 12 months.

One thousand eight hundred forty-five women (1,255 were eligible for the endometrial safety population; 726 comprised the vasomotor symptoms substudy) were randomized over a period of nearly two years to receive either daily estradiol (mg)-progesterone (mg) (1/100, 0.5/100, 0.5/50, or 0.25/50), or placebo. The average age was 55 years and BMI 27.

No endometrial hyperplasia was observed at the end of 12 months, while single dose estradiol-progesterone capsule (1 mg/100 or 0.5 mg/100 estradiol and progesterone) provided significant relief from vasomotor symptoms and improvement in the MENQOL domain was observed. Women reported a reduction in hot flashes as early as four weeks of treatment.

The researchers concluded, “This estradiol-progesterone formulation may represent a new option, using naturally occurring hormones, for the estimated 3 million women using nonregulatory-approved, compounded hormone therapy.” Although, currently there is no evidence that bio-identical hormones are superior to synthetic hormones.

Dr. James Liu, M.D., President of the North American Menopause Society and Chairman of the Department of Obstetrics and Gynecology, UH Cleveland Medical Center said, “The approval of BIJUVA represents an important, novel and effective treatment option for women and their healthcare providers to manage the vasomotor symptoms of menopause.”

Bijuva is expected to hit the US markets in the second quarter of 2019. According to the U.S. Census Bureau, about 43 million American women are of the menopausal age of between 45 and 64, and some 80 percent of all menopausal women experience symptoms like hot flashes and night sweats.

The most common side effects are breast tenderness, vaginal discharge and spotting, headache, and pelvic pain.

Bijuva comes with a boxed warning for cardiovascular disorders, breast cancer, endometrial cancer, and probable dementia.

FDA press release

TherapeuticsMD press release

REPLENISH Trial

Abstract

News from NAMS 2018: Estetrol, the next generation hormone therapy linked to significant improvement in menopausal VMS

Estetrol (E4) (Donesta®) in daily oral dose of 15 mg appears to be the most effective dose for the treatment of menopausal VMS reports the results of Phase IIb (E4 Relief) clinical trial presented at the 29th Annual Meeting of the North American Menopause Society (NAMS), being held on 3-6 October 2018 in San Diego, CA.  

Estetrol (E4) is the first promising NEST™ or Native Estrogen with Selectively action in Tissues produced by the human fetal liver, crossing the placenta and excreted in maternal urine at relatively high levels during pregnancy. It has a half-life of 28 hours and exhibits a unique mode of action.

It acts as an estrogen agonist in the vagina, endometrium, bone, and cardiovascular system and shows a mixed agonist and antagonist estrogenic property in liver and breast tissue. This results in lower level of breast stimulation with no effect on hemostasis parameters and triglycerides levels.

This multicentric, randomized, placebo-controlled, double-blinded, dose-finding study Phase IIb clinical trial recruited post-menopausal women, aged 40-65years across many European countries. Women qualified to participate in the trial if they had ≥7 moderate to severe hot flushes (HF) per day, or ≥50 moderate to severe HF in the week and Transvaginal Ultrasound (TVUS) showed a bi-layer endometrial thickness ≤5 mm.

Women were randomized to receive 2.5; 5; 10; or 15 mg E4, or placebo, once-daily, for 12 weeks. The primary endpoints were decreased in frequency and severity of hot flashes (VMS), while effects on genitourinary symptoms, lipid and glucose metabolism, hemostatic and bone markers were secondary endpoints of interest. Menopause Rating Scale (MRS) assessed the health-related quality of life. Safety of the drug was assessed by measuring the endometrial thickness and bleeding episodes while on therapy. 

As a protective measure against endometrial hyperplasia, the patients receive 2 weeks of progestin therapy (Dydrogesterone 10 mg) after the cycle of E4 is complete.

Of the 257 women selected, 200 women completed the study. At the end of the study period, there was an 80% improvement in frequency and severity of hot flashes, vaginal dryness, and dyspareunia in the E4 15mg group as compared to placebo. The improvement in VMS started as early as the end of 2 weeks with a trend reaching significance at the end of 4 weeks.

All the 11 dimensions of MRS also showed improvement with a near 50% reduction in the total score. The drug was completely safe with no effect on total triglycerides and cholesterol panel, hemostatic parameters and endometrial hyperplasia.

Estetrol (E4) (Donesta®) could be the next breakthrough for treatment of the full spectrum of menopausal symptoms. It is wholly natural and safety profile differs from that of estrogen. It could be the next oral alternative for transdermal estrogen preparations because of more breast safety.

Maud Jost, E4 Program Director, commented: “The presentation of data from the E4 Relief trial provides further evidence of the potential of Estetrol in the treatment of menopausal symptoms. This is the second-high profile conference where our compelling data from our promising Donesta program is presented. Preparations are already underway to progress Donesta into Phase III trials, which if approved could provide an innovative alternative to the millions of women seeking treatment with an improved benefit and risk profile.” 

Mithra (Euronext Brussels: MITRA), is a company specialized in Women’s Health is headquartered in Liège, Belgium.

Press release

Abstract S-16

Product page

Ob/Gyn Updated Facebook page

Media Courtesy: www.Mithra.com

News from NAMS 2018: Interferential current relieves dyspareunia in women with Premature ovarian insufficiency

www.mccc.edu

Women who have premature ovarian insufficiency (POI) face an array of problems including infertility, an early risk of a CVD event, vulvovaginal atrophy (VVA) and painful sexual intercourse due to insufficient estrogen levels. Dyspareunia is still reported while on HRT and limits the ability to enjoy sex and achieve orgasm.

Vaginal estriol cream is the most commonly prescribed treatment to increase lubrication and relieve the symptoms associated with estrogen deficit.

A new form of treatment with the help of Interferential current now offers hope by improving lubrication; thereby, reducing pain and increased the frequency of satisfying sexual encounters.

Researchers from the University of Campinas, commonly called Unicamp, in São Paulo, Brazil recruited women between the ages of 18 and 50 with POI and taking HRT for this small RCT. Initially, 80 women were selected out of which 35 included in the study. The women were asked to fill out a sexual function questionnaire (FSFI) and randomized to receive either Interferential current (IC) compared to topical estrogen cream (E).

IC group received electrical stimulation of the pelvic floor, in a total of 8 sessions of 20 minutes each for a month. Women in the E group used .5mg of topical estrogen per day for four weeks.

The researchers looked at improvements in lubrication and sexual function score, and relief from pain during physical intimacy. Data analysis showed that while lubrication and dyspareunia improved significantly in both the groups, there was not much improvement in the FSFI scale for women on local estrogen therapy.

However, there was a significant improvement in pre and post-intervention FSFI scores among women who received interferential current therapy (p=0.0004). These women also reported a significant improvement in sexual satisfaction and frequency of orgasm thus enabling the increase in sexual activity.

“We were encouraged with these results as they reveal a new alternative for the treatment of sexual complaints,” says Dr. Helena Giraldo, lead author of the study.

“Although this was a small study, it opens the door for further research that will help identify more options for women to help improve their overall quality of life by making their sexual experience more enjoyable,” says Dr. JoAnn Pinkerton, NAMS executive director.

The study was also presented at the 18th World Congress of Gynecological Endocrinology in Florence, Italy.

Abstract S-17

NAMS press release 

Ob/Gyn Updated Facebook page

North American Menopause Society (NAMS) video series about important midlife health topics: Nonhormone Prescription Options for Hot Flashes

The North American Menopause Society (NAMS) provides practical information on important midlife health topics for women. All the interviews in the series are hosted by NAM Board of Trustees Member and Immediate Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

HRT remains the most effective solution for the relief of menopausal hot flashes but not all women want to use hormones, or it may be contraindicated in some as women with breast cancer. Fortunately, there are some non-hormonal therapy that provide some relief, although they may not be as effective as estrogen.

In this informative video of 2018 series, Dr. Shapiro interviews Dr. James Simon, Clinical Professor, Department of Obstetrics and Gynecology, the George Washington University School of Medicine. Dr. Simon explains the efficacy of nonhormone options for hot flashes.

Ob/Gyn Updated Facebook page

What should midlife women know about preventive cardiology?

We are all aware that sex and gender differences are important in the diagnosis and management of cardiovascular diseases. A woman’s risk of a cardiac event and stroke sharply increases after the onset of menopause. Here is an informative video regarding preventing and managing the increased risk of a cardiac event after menopause.

Dr. Beth Abramson is a preventive cardiologist and helps women manage the risk of heart disease.  In this video by North American Menopause Society (NAMS), she answers many vital questions about menopausal hormone therapy, midlife weight gain, smoking, alcohol, and aspirin therapy.  

North American Menopause Society (NAMS) video series about important midlife health topics: Hormones and Breast Health

The North American Menopause Society (NAMS) is proud of its comprehensive video series for women on important midlife health topics. All the interviews in the series are hosted by NAM Board of Trustees Member and Immediate Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

In this video of 2018 series, Dr. Shapiro discusses the very controversial topic of hormones replacement therapy (HRT) and breast cancer with Dr. Stephanie Faubion, Director, Office of Women’s Health at the Mayo Clinic, Rochester, Minnesota.

HRT remains the most effective solution for the relief of menopausal symptoms and is also effective for the prevention of osteoporosis. It is thought to be associated with increased risk of stroke and breast cancer, but the risk has not been yet quantified. Dr. Faubion talks about HRT in various clinical settings, including women who have a family history of breast cancer and those with BRCA mutations.

Ob/Gyn Updated Facebook page

New oral drug treatment found highly effective in reducing menopausal hot flashes

A neurokinin 3 receptor (NK3R) antagonist (MLE4901) rapidly reduced hot flashes for short and long-term in postmenopausal women; thus, eliminating the need for estrogen therapy report researchers from Imperial College London. The study was published on March 12, ahead of print in North American Menopause Society Journal Menopause.

The neurokinin 3 receptor (NK3R) antagonist (MLE4901) is manufactured by Millendo Therapeutics Inc, based at Ann Arbor, Michigan.

Nearly 73% of postmenopausal women experience hot flashes with disruptive effects on activities of daily life along with increased use of hormonal medications. Although estrogen is crucial for the maintenance of bone and cardiovascular health during menopausal years, the maximum efficacy takes weeks to develop and women often discontinue the estrogen therapy for fear of side effects. 

In this phase 2, randomized, double-blind, placebo-controlled, single-center, crossover trial (NCT02668185) the researchers recruited 37 women between the age of 40 to 62 years, experiencing ≥7 HF/24 hours to receive either NK3R antagonist MLE4901 40mg bd for 4 weeks or placebo 40 mg bd in random order.

After a gap of 2 weeks, the women received another drug which they didn’t receive first time for4weeks.

The oral NK3R antagonist MLE4901 not only reduced the frequency of hot flashes by 72% by day 3 of treatment but also reduced the severity of HF by 38% (44% by end of 4 weeks) as compared to baseline symptoms (all P < 0.0001).

The interference due to HF was also reduced by 61% (70% by end of 4 weeks) and level of bother by 39% (50% by end of 4 weeks) at the end of 3 weeks of treatment as compared to a placebo.

Professor Waljit Dhillo, the lead author of the study said: “If a woman is having more than seven flushes a day and the drug is getting rid of three-quarters of them, that’s pretty life-changing.

“For day to day living and work, that’s a significant impact on quality of life. If we can reduce flushing by 73 percent it’s a game-changer for those patients,” he further added.

JoAnn Pinkerton, MD, executive director of The North American Menopause Society opined that further large-scale trials to bring the drug into clinical practice would be game-changing for women with a history of estrogen-dependent cancers like breast and uterine cancers.

"Relief of hot flashes is an important, unmet need for these women, as other nonhormonal therapies such as low dose antidepressants or gabapentin have not been as effective as hormone therapy at relieving severe hot flashes," she further added.

She also suggested looking at the long-term effect of this drug, specifically after continued use for 3-5 years as some women continue to experience HF for 15-20 years past menopause.

Abstract

Media courtesy: Getty Images

North American Menopause Society (NAMS) video series about important midlife health topics: Clinical options for treating GSM

The North American Menopause Society (NAMS) is proud of its comprehensive video series for women on important midlife health topics. All the interviews in the series are hosted by NAM Board of Trustees Member and Immediate Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

In this first video of 2018 series, Dr. Shapiro discusses clinical aspects of the genitourinary syndrome of menopause (GSM) with Dr.Nick Panay, an obstetrician-gynecologist from London and general secretary-elect of the international menopause society(IMS).

This is a very common problem worldwide, but it is severely underreported and undertreated because most of the women are reluctant to come forward and discuss it with the health care providers.

In this video, Dr. Panay discusses treatment options for women with GSM.

Do not use HRT solely for primary prevention of chronic diseases: USPSTF final recommendation

The US Preventive Services Task Force (USPSTF) recommends against the use of HRT in asymptomatic post-menopausal women solely for preventing chronic diseases in its final statement published yesterday in JAMA.

The recommendation holds good for estrogen alone or combined with progestin and upholds the previous 2012 statement.

The USPSTF statement does acknowledge few benefits of HRT in postmenopausal women such as reducing the risk of fractures and diabetes, but the potential harms outweigh the moderate benefits cited.

Combined use of estrogen and progestin is associated with increased risk of invasive breast cancer, coronary artery disease, venous thromboembolism, stroke, dementia, gallbladder disease, and urinary incontinence.

Use of estrogen alone predisposes the women to greater risk for thromboembolism, stroke, dementia, gallbladder disease, and urinary incontinence.

The recommendations were based on evidence from  Women's Health Initiative (WHI) trials, which were stopped early because of sufficient evidence of serious adverse effects in postmenopausal women.

The USPSTF statement is accompanied by an editorial by Cora E. Lewis, MD, MSPH, from the Division of Preventive Medicine at University of Alabama at Birmingham School of Medicine, and Melissa F. Wellons, MD, MHS, from the Division of Diabetes, Endocrinology and Metabolism at Vanderbilt University Medical Center in Nashville, Tennessee says that although the WHI trial was a observational study, till date no large sufficiently powered trials exist to recommend against the WHI conclusions.

The authors further asserted that these recommendations do not apply to “women who are considering hormone therapy for the management of menopausal symptoms, such as hot flashes or vaginal dryness. It also does not apply to women who have had premature menopause (primary ovarian insufficiency) or surgical menopause.”  

Also, the route of administration considered in the study is oral or transdermal and not creams and rings because those are not generally used for primary prevention of chronic conditions.

The editorial also mentions about the “timing hypothesis” put forward by the American Association of Clinical Endocrinologists/American College of Endocrinology in its July 2017 updated guidelines on menopause.

USPSTF statement stats that there is not sufficient evidence to support the “timing hypothesis” at present. It requires very large, sufficiently powered studies to evaluate the risk/benefit ratio in this specific age group.

At present, few women are on HRT, and physicians consider HRT only for the treatment of menopausal symptoms. Relatively healthy, younger menopausal women with severe climacteric symptoms may be prescribed HRT for symptoms relief and not for chronic disease prevention.

Full Text of  USPSTF guidance
 Editorial

Easing the menopause transition by latest technology- upcoming North American Menopause Society (NAMS) 2017 Annual Meeting.

The upcoming NAMS 2017 annual meeting that will be held at Philadelphia October 11-14 is sure to be an academic feast. The scientific session will bring in all the latest and comprehensive updates from world renowned speakers with focus on the technological advances that can help women in seemingly smooth transition through the menopausal years.

The meeting is going to kick start with a pre-meeting symposium about Musculoskeletal Health in Postmenopausal Women: Assessment and Management of Fracture Risk by Co-Chair, Michael R. McClung, MD.  This symposium will cover assessment of postmenopausal osteoporosis; including dual-energy x-ray absorptiometry(DXA) best practices and new imaging modalities. It will also cover the new pharmacological therapies for osteoporosis and ways to improve the muscle functions.

This will be followed by President’s Reception and other CME activities. The topics that are expected to be covered include: Vaginal Health and Pelvic Pain, Hormone Therapy, Uterine Bleeding and Adnexal Masses, Lesbian Health and Sexuality, Cardiovascular Disease Risk Factors, Migraines and Mood Disorders in Midlife Women, Advances in Breast Imaging, Musculoskeletal Health Concerns, Social Media and Technology: Driving the Direction of Women’s Health and Update on MsFLASH Trials.

The NAMS updated position statement on Hormone therapy will be presented by JoAnn Pinkerton, MD, from the University of Virginia in Charlottesville, who is executive director of NAMS.

The findings of WHI follow -up study published in JAMA, played a key role in supporting some of the recommendations.

Technological advances, especially mobile health technology and its role in improving patient’s engagement and health will also be focused upon.

In all, the meeting will engage a diverse, multiracial, multiethnic and multispecialty group of people with varied interests, but there will be something for everyone.

Looking forward seeing latest updates and good clinical research abstracts from the meeting.

Related Links

WHI Study: No increased all-cause mortality with menopausal hormone therapy

On World Contraceptive day: Review of contraception during perimenopausal years.

September 26^th is World Contraceptive day, it is annual worldwide campaign to improve global awareness about contraception, with the dream that every pregnancy is intentional.

RCOG has released a review paper about contraceptive methods around menopause, published today in RCOG journal The Obstetrician and Gynecologists. The WHO defines the menopause as permanent cessation of menstruation caused by the loss of ovarian follicular activity, which is essentially a retrospective diagnosis.

There exists no accurate biological marker that defines the moment when the woman ceases to be fertile.  During the perimenopausal years menstrual irregularities are very common with irregular scanty or heavy blood loss.

Although after 30’s natural fertility is on decline, effective contraception should still be used till menopause to avoid unintended pregnancies.

Some important key contents of this review paper on perimenopausal contraception are:

No method of contraception is contraindicated based on age alone, up to the age of 50 years, HRT does not provide adequate contraception as it inhibits ovulation in only 40% of women.

Some hormonal contraceptive also helps in relieving common perimenopausal gynecological problem.  Contraception must be used alongside HRT to avoid unplanned conception. Progestogen-only methods and intrauterine contraception (IUC) are suitable.

During the perimenopausal years, in women over the age of 50 years not using hormonal methods, contraception can be stopped after 1 year of amenorrhea as fertility is unlikely to return, while in women under 50 years of age, contraception should be continued for 2 years, as the return of fertile ovulation is more likely to occur.

The Faculty of Sexual and Reproductive Healthcare (FSRH) recommends that contraception should be continued for 1 year after recording two FSH levels at >30 IU/l, taken at least 6 weeks apart.

Alternatively, women can consider stopping their method of contraception at the age of 55 years when most will have reached natural infertility.

Women must be advised on all available methods of contraception, including long-acting reversible methods (LARC), so they can make an informed choice.

Combined oral contraception have the advantage of regular bleeding pattern and relief in hot flushes, but increased risk of thrombosis, and breast and cervical cancer. Some women prefer progesterone only pills because it is contraindicated in few medical conditions but irregular bleeding is a problem.

Progesterone only injectables are long acting but they often mask menopause, causes loss of BMD and once injected cannot be removed.

Copper intrauterine device and Levonorgestrel-releasing device are unsuitable if women have irregular uterine cavity.

Barrier methods are best, without any side effects and can be safely used till menopause.

Women can also avail emergency contraception in the perimenopausal age group. Levonorgestrel an oral progestogen; ulipristalacetate (UPA) an oral selective progestogen receptor modulator; and the copper IUD can be used in emergency.

Contraceptives of future: Frameless IUDs and Intrauterine ball has recently been licensed in Austria and will likely be marketed elsewhere in Europe and North America. It is a frameless IUD consisting of a shaped memory alloy (Nitinol^®) thread that holds 20 tiny copper spheres. The device becomes spherical once delivered into the uterus and might have greater potential for use in non-uniform endometrial cavities. As a hormone-free method, there will be no contraindications to its use in perimenopausal women.

http://newatlas.com/intra-uterine-ball-iub/23534/

Microchip drug-release technology is currently under development and will allow a progestogen-releasing microchip to be implanted for up to 16 years of use, which can be switched on and off with a remote control.

http://news.mit.edu/2015/implantable-drug-delivery-microchip-device-0629

Researchers are working on vaginal ring releasing UPA, a selective progesterone receptor modulator that will provide estrogen free contraception.

Not much progress has been made in areas of male contraception and condoms and sterilization are only current methods available.

Full Text

Endocrine Society issues guidelines for management of menopausal symptoms in breast cancer survivors

Women experiencing menopausal symptoms after receiving treatment for breast cancer should be managed with life-style changes instead of hormonal therapy says the first ever set of professional guidelines issued by the Endocrine Society.

Increasing incidence of breast cancer and improved survival have led to increasing number of women survivors who have a long life ahead, while experiencing the side effects of cancer chemotherapy.  

It is estimated that there are 9.3 million breast cancer survivors worldwide, who experience menopausal symptoms or clinical manifestations of estrogen deficiency.

The comprehensive review was published August 02, 2017 in Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Premenopausal women diagnosed with breast cancer experience abrupt onset of estrogen depletion symptoms after treatment with chemotherapy. Just like women experiencing natural menopause these women develop vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), osteopenia, and osteoporosis, CVDs and psychological symptoms like sleep disorders, mood changes and depression.

These women cannot be treated with Hormonal Replacement Therapy (HRT) like their counterparts with natural menopause.

The study’s first author, Richard J. Santen, M.D., of the University of Virginia Health System in Charlottesville, VA said in a News Release by Endocrine Society “Following breast cancer, women should generally not be treated with menopausal hormone therapy but should instead focus on lifestyle modifications such as smoking cessation, weight loss, and regular physical activity.”

“Pharmacologic agents are also available to treat women with severe symptoms. The most important thing to remember is that therapy must be individualized based on each woman’s needs and goals,” he further added.

The author and his colleagues reviewed randomized controlled clinical trials (RCTs), observational studies, evidence- based guidelines, and expert opinion from professional societies to formulate the guidelines.

1) Life style modification advised for all breast cancer survivors include weight management, regular physical activity, smoking and alcohol cessation, vitamin D and calcium supplementation and eating healthy diet.

2) Sleep and other psychomotor symptoms should be treated with mind-brain-behavior or nonhormone, pharmacologic therapy.

3) Vasomotor symptoms respond well to selective serotonin /noradrenaline reuptake inhibitors and gabapentenoid agents.

4) A variety of non-hormonal treatments are available for treating osteoporosis like bisphosphonates, including zoledronic acid (Reclast) and denosumab (Prolia).

5) Treatment of VVA is a grey zone, low dose estrogen applied vaginally is absorbed in blood and although the blood levels are within normal limits, it could still potentially stimulate occult breast cancer cells. Hence, it is not generally advised, especially those on aromatase inhibitors.

6) Intravaginal DHEA and oral ospemiphene is often prescribed to relieve dyspareunia but their safety is still not established in breast cancer survivors.

7) Vaginal laser therapy is being used, but still more data is needed to document its efficacy.

8) Researchers are looking into other therapies in near future like lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol.

9) The most important recommendation is treatment should be individualized according to need of each patient.

New study reassures postmenopausal women about safety of vaginal estrogen.

Postmenopausal women using vaginal estrogen are not at increased risk of cardiovascular disease and cancer reports the result of study published August 14, 2017 in Menopause.

This is another important study conducted using data from Women's Health Initiative(WHI) observational study which tracked the medical history and health habits of 93,676 women nationwide for 8-12 years. The current study recruited 45,663 women between 50-79 years of age, across 40 US clinical centers. These women did not use systematic estrogen and underwent a median follow-up of 7.2 years.

Results of this prospective observational cohort study showed that in women with intact uterus and using vaginal estrogen, the risk of cardiovascular event, pulmonary embolism, stroke, invasive breast cancer, endometrial and colorectal cancer does not exceed the risk faced by non-hormone users.

Women using vaginal estrogen had 32% lower risk of global index event (GIE), defined as time to first occurrence of coronary heart disease (CHD), invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, or death from any cause as compared to non-users (GIE adjusted hazard ratio 0.68, 95% confidence interval 0.55-0.86).

Surprisingly, in Hysterectomized women the composite risk of GIE or individual event did not differ much among users and non-users (GIE adjusted hazard ratio 0.94, 95% confidence interval 0.70-1.26).

Based on the results of this trial, US FDA is considering a proposal to revise the warning labels on low dose estrogen packaging to incorporate the safety profile of vaginal estrogen.

Current labels were approved before any evidence was put forth about safety of vaginal estrogen and it may discourage patients from using topical estrogen which are safe and highly effective in treatment of genitourinary symptoms of menopause. 

Different formulations like topical creams, an intravaginal insert, and an intravaginal ring have the same safety and efficacy.

JoAnn Pinkerton, MD, executive director, North American Menopause Society (NAMS), said in a  position statement released by North American Menopause Society on August 17, “These findings should reassure women and their healthcare providers that low-dose vaginal estrogen, which keeps blood levels within the normal postmenopausal range, is effective and safe for postmenopausal women who need relief from only vaginal symptoms,” says Dr. JoAnn Pinkerton, NAMS executive director. “The boxed warnings about the risk of heart disease, stroke, blood clots, and cancer do not apply to these low-dose vaginal therapies. Instead, women who experience bleeding or those with breast cancer should include their healthcare providers and oncologists in deciding about this option.”

Access the Abstract, NAMS position statement.

Clinical review: Updates on Menopause

Here is a roundup of the latest research on Menoapuse.

In this article:

Early menopause ups the risk of developing type 2 diabetes

Women who have an early natural menopause have 2.5 times the risk of developing type 2 diabetes as compared to women who have normal menopause reports the results of a large population based study published online July 18, 2017 in Journal Diabetologia.

https://obgynupdated.blogspot.com/2017/07/early-menopause-ups-risk-of-developing.html

Oophorectomy during premenopausal hysterectomy: Evaluating the prevalence

Nearly 1 in 3 women undergo oophorectomy during premenopausal hysterectomy in absence of appropriate indication, reports a study published ahead of print May 8, 2017 in North American Menopausal Society (NAMS) journal Menopause.

https://obgynupdated.blogspot.com/2017/06/oophorectomy-during-premenopausal.html

Loss of estrogen in postmenopausal women puts them at high risk for lumbar disc degeneration.

Declining estrogen levels during perimenopausal and menopausal years is associated with severe lumbar disc degeneration reports a study published online June 12, 2017 in journal Menopause, the journal of The North American Menopause Society (NAMS).

https://obgynupdated.blogspot.com/2017/06/loss-of-estrogen-in-postmenopausal.html

ACP updates guideline for treating Osteoporosis.

According to International Osteoporotic Foundation (IOF), 1 in 3 women over age 50 will experience osteoporotic fractures and nearly 200 million women suffer from osteoporosis worldwide.

https://obgynupdated.blogspot.com/2017/05/acp-updates-guideline-for-treating.html

Polycystic ovarian syndrome increases the risk of subsequent early ovarian aging later in life.

Women with polycystic ovarian syndrome (PCOS) have 8.64-fold increase in risk of developing premature ovarian failure as compared to women who did not have PCOS according to a population based study in forthcoming issue of Journal Menopause. Metformin was found to be effective in reducing such risk.

https://obgynupdated.blogspot.com/2017/05/polycystic-ovarian-syndrome-increases.html

New natural (bioidentical) 17ß-estradiol-progesterone combination available as single soft gel capsules effective in treating postmenopausal symptoms: News from ENDO17

An innovative, investigational combination of 17ß-estradiol and progesterone in a single, oral softgel, was found effective for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. The results of the study were presented at the ENDO 2017, the annual meeting of the Endocrine Society in Orlando, Florida, April 1-4.

https://obgynupdated.blogspot.com/2017/04/new-natural-bioidentical-estrogen.html

New class of drug effective in targeting menopausal symptoms: News from Endocrine Conference 2017.

A new class of drug Neurokinin 3 (NK3) receptor antagonists is highly effective and low risk alternative to hormone replacement therapy(HRT) for treatment of menopausal hot flashes according to a study presented at the ENDO 2017, The endocrine society annual meeting from April 1–4, 2017, in Orlando, FL.

https://obgynupdated.blogspot.com/2017/04/new-class-of-drug-effective-in.html

Menarche ≤11 years and Nulliparity is a risk factor for Premature and Early Menopause.

Women who had their first period at or before the age of 11 are at increased risk for premature and early menopause and the risk is further amplified if the woman is nulliparous according to a large observational study published on January 25, 2017 in Oxford Journal of Human Reproduction.

https://obgynupdated.blogspot.com/2017/03/menarche-11-years-and-nulliparity-is.html

North American Menopause Society (NAMS) video series about important midlife health topics: Hormone therapy timing hypothesis and cognition

In this latest video, Hormone Therapy and Cognition, Dr. Shapiro interviews Dr. Pauline Maki, Past President of NAMS, Professor of Psychiatry and Psychology, Director of Women’s Mental Health Research, and Research Director at UIC Center for Research in Women and Gender at the University of Illinois at Chicago. Dr. Maki discusses the hormone therapy timing hypothesis and cognition, the relationship between cognition and cardiovascular protection, and the latest cognition trials and studies.

Timing of initiation of hormone therapy in relation to age or time since final menstrual period modify the effect of hormone therapy on cognition as documented now by three very well-known clinical trials. Dr. Maki explains the timing hypothesis very well in this latest NAMS video.

North American Menopause Society (NAMS) video series about important midlife health topics:Individualizing Hormone Therapy

The North American Menopause Society (NAMS) has started comprehensive video series for clinicians about important midlife health topics. All the interviews in the series are hosted by NAMS Board of Trustees Member and President Dr. Marla Shapiro, a Canadian physician, who led this exciting initiative.

In this video The North American Menopause Society answers questions about individualizing hormone therapy—its history, recommendations, timing hypothesis, and routes of administration. Dr. Schnatz also discusses the concept of the appropriate dose with the appropriate route for the appropriate duration.