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

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

www.urmc.rochester.edu

Menopausal hormone therapy with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) did not increase all-cause mortality and disease specific mortality in participants of Women’s Health Study(WHI) after nearly 2 decades of follow-up says the results of new data analysis published online in JAMA.

This study is specifically important because earlier studies have never looked into disease specific and all-cause mortality of women receiving hormone therapy. Menopausal hormone therapy is debated since decades, and the interest in prescribing HT waxes and wanes as new data is published.

The researchers analyzed data from two studies:  the first study was estrogen with progestin trial and the second was estrogen only trial published in JAMA in 2002 and 2004 respectively.

The researchers conducted an extended follow-up of women included in this trial for 18 years. The combined trial included 16,608 women with a uterus while the estrogen only trial included 10,739 women with a history of hysterectomy.

In the estrogen+ progesterone group, 8506 women were randomized to receive HT and 8102 were given placebo for a median of 5.6 years. In estrogen only group, 5310 women took estrogen and 5429 were placed on placebo for a median 7.2 years.

For the current analysis, the researchers pooled the data from these 2 studies, amounting to a total of 27,347 women, with ages between 50 to 79 years and 80.6% being white. These women were followed up for 18 years. There were 7489 deaths through December 31, 2014, including 1088 during the trial and 6401 since the trials ended.

All-cause mortality did not defer between the two study arms, it was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort. The figures were similar for cardiovascular and cancer mortality.

The only difference in mortality was observed for breast cancer, with estrogen+ progesterone group facing a 44% increased risk relative to placebo while estrogen was protective against breast cancer and reduced the risk by 45%. 

Both the earlier trials were stopped early when it became clear that HT did not improve the CVD outcomes as for both trials the primary outcome was prevention of chronic diseases and not to gauge the effectiveness of HT in managing menopausal symptoms.

Hence, the results of the study are especially important as they reassure the physician and patient that HT can be safely used for management of menopausal symptoms with a positive risk/benefit profile.

At the same time, it should also be noted that HT increases risk of stroke and breast cancer and decreases risk of endometrial and uterine cancer and hip fractures.

Still, the results of the study cannot be applied in every situation and for all women. Women who are at high risk for blood clots and breast cancer, the added increased risk may outweigh the benefit of alleviating menopausal symptoms individually.

The article is accompanied by an editorial by Melissa McNeil, MD, MPH, from the University of Pittsburgh in Pennsylvania which highlights the complexity of the issue. She writes, "Although the long-term data on total and cause-specific cumulative mortality of pooled data for hormone users vs nonusers is both compelling and reassuring, several questions remain. Perhaps the most challenging question involves the issue of whether there is a difference in overall mortality by age and menopausal status at the time of initiation of hormone therapy."

"This reduction in mortality...thus remains suggestive but not definitive," Dr McNeil further added. 

"Other questions that remain include the optimal duration of hormone therapy and if an even earlier initiation of hormone therapy, such as within 2 years of the menopausal transition, would provide additional benefits."

So, the takeaway from the study results is: HRT can be prescribed to treat menopausal symptoms with a positive risk-benefit profile without increasing all cause, cardiovascular and cancer mortality. It however should not be prescribed for prevention of  CVD and other chronic conditions.

The authors have disclosed no relevant financial relationship.

Menopausal hormone therapies and the risk of stroke varies with route of administration

Courtesy: menopausemoxie.com

Route of menopausal hormone therapy plays a very important role in increasing or decreasing the risk of stroke in postmenopausal women reports the results of large Danish national historical study. The study was originally  published in June 2017 in Journal Stroke.

Randomized trials have shown an increased risk of stroke and the study was not completed because of higher risk faced by study participants.

This large epidemiological study included nearly all women aged 51 to 70 years living in Denmark and the cohort was recruited by linking 5 Danish registries, that provided data about hormone therapy exposure and stroke diagnoses (ischemic/hemorrhagic/subarachnoid hemorrhage).

Of, nearly a million women included in the study, 36% used hormone therapy. 2% women (20 199) suffered a stroke.

Current users of hormones were 16 % at increased risk of stroke as compared to never users (RR) 1.16 (95% CI 1.12–1.22), but the risk of hemorrhagic stroke decreased RR: 0.80 (95% CI, 0.70–0.91).

Users of oral continuous, cyclic combined estrogen/progestin, and estrogen only were at 29%, 11% and 18% more at risk respectively for all strokes as compared to never users. The increased risk was because of ischemic stroke, but not hemorrhagic stroke.

Transdermal HT is safer and does not lead to increased risk of stroke. Unopposed transdermal estrogen therapy had a protective effect, it decreases the risk by 18% (RR 0.82; 95% CI 0.69-0.98).

Vaginal HT was also protective and decreased the risk of stroke by 35% (RR 0.65; 95% CI 0.59-0.70).

Tibolone use increased the stroke risk by nearly 30%, including haemorrhagic.

The authors concluded that, “we found an increased risk of stroke, based on ischemic stroke, with oral hormone therapies that was comparable to findings from randomized studies. We found no risk of stroke with transdermal application and a reduced risk with vaginal estrogen.”

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).

According to the National Institutes of Health (NIH), 80 percent of adults will experience lower back pain sometime during their lives, and during any given three-month period, 25 percent of us will complain of pain in that area.

Intervertebral disc degeneration is one of the most common mechanical cause of lower back pain and it is so common that it is sometimes considered a normal part of aging.

Many studies have documented an association between estrogen deficiency and disc degeneration and benefits of Hormone Replacement Therapy (HRT) in maintaining the lumbar disc height in post-menopausal women. This study is unique because it has included age matched men as comparison group.

The study was carried out in China and the study cohort consisted of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016.

Demographic of both groups were obtained along with information on years since menopause (YSM). All participants received a MRI to evaluate the spine.

During the younger years, men were more prone to disc degeneration as compared to age matched women (P < 0.05).

As men and women aged, postmenopausal women were significantly more prone to develop more severe disc degeneration than age-matched men (P < 0.05) and premenopausal and perimenopausal women (P < 0.01).

The most severe degeneration was seen within the first 15 years of menopause at all disc levels from L1 to S1.

Dr. JoAnn Pinkerton, executive director of NAMS says “This study shows that menopause is associated with more severe disc degeneration, Prevention of disc degeneration of the lumbar spine may be another potential benefit for symptomatic menopausal women who may be candidates for hormone therapy.”

The authors call upon more studies to determine whether age or estrogen deficiency is responsible for the progression of disc degeneration at lumbar spine. 

Hormone replacement, Insulin sensitivity and Diabetes: Is there a critical window of opportunity?

This article is based on a commentary Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital and   a recent paper published in Journal of Clinical Endocrinology & Metabolism by Pereira R et al which concluded that there certainly is a time period in postmenopausal women when giving estrogen would alter the development of Insulin resistance and subsequent T2DM.

Pereira and colleague conducted a very small and short term RCT consisting of 46 postmenopausal women. Half of the subjects were less than 6 years into menopause and the other half were older and nearly 10 years past menopause.

All these women were given transdermal estradiol in high dose of 150 µg/day for a week.

After that they were given Glucose disposal rate ( GDR)  test which measures the rate of glucose uptake from the blood by the peripheral tissues, such as skeletal muscle with a hyperinsulinemic-euglycemic clamp.

There is no apparent time dependent decline in GDR with age or menopausal status per se. But, it was seen that after estrogen therapy  in younger women with less than 6 years into  menopause, a improvement in GDR and insulin sensitivity was observed , whereas those women who are older and further down the lane from menopause there was deterioration in GDR test and decrease in insulin sensitivity.

In the past there are several Randomized Control trials studying the effect of hormone therapy on diabetes in menopausal women. The data from the Heart and Estrogen/progestin Replacement Study (HERS), in which 2763 postmenopausal women with documented coronary heart disease (CHD) were randomly assigned to daily estrogen plus progestin therapy or to placebo showed that those assigned to hormone therapy had a 35% lower risk of diabetes.

Similarly two trials from the Women’s Health initiative also showed benefits, although the effect was smaller when using estrogen and progesterone as when using estrogen alone.

Now does that mean that HRT should be solely started to prevent the happening of diabetes? No, because HRT is associated with its own risks of venous embolism and stroke.

The study simply gives us one more reason to be optimistic and instrumental in starting HRT in those recently postmenopausal women who have other indications for hormone therapy, such as hot flashes and other symptoms where hormone therapy would be indicated. The study also points to important metabolic benefits of hormone therapy that should be studied in greater details with much larger trials. 

References:

Pereira RI, Casey BA, Swibas TA, et al. Timing of estradiol treatment after menopause may determine benefit or harm to insulin action. J Clin Endocrinol Metab. 2015;100:4456-4462. Abstract

Margolis KL, Bonds DE, Rodabough RJ, et al.; for the Women's Health Initiative investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative hormone trial. Diabetologia. 2004;47:1175-1187. Abstract

Kanaya AM, Herrington D, Vittinghoff E, et al.; for the Heart and Estrogen/progestin Replacement Study investigators. Glycemic effects of postmenopausal hormone replacement therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:1-9.

http://www.ndei.org/Glossary/Glucose_disposal_rate/

http://care.diabetesjournals.org/content/30/5/1143.full

Guidelines advocate a more tailored approach in management of Menopause!

Guidelines advocate a more tailored approach in management of Menopause!

photo courtesy -dreams time

The evaluation and treatment of menopause has undergone a sea change in last two decades, but this was not always backed up by evidence.

The Endocrine Society has updated the latest guidelines, and the recommendations are all backed by solid clinical research. The guidelines were published online October 7 and appeared in the November issue of the Journal of Clinical Endocrinology & Metabolism.

The article is primarily derived from the journal article “Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline.” In the November issue of The Journal of Clinical Endocrinology & Metabolism 2015 100:11, 3975-4011

In 2002, a large government study called the Women’s Health Initiative study generated intense scrutiny on the practice of menopausal hormone therapy due to concerns about increased risk for blood clots, stroke, breast cancer and heart attacks. Since then, physicians all over the world are very cautious in prescribing hormones as a therapy for management of menopausal symptoms.

The guidelines advocates that the individual risk is lower in younger women who have recently gone through menopause, and varies based on a woman’s health history, age and other factors. Developed by Endocrine Society menopause experts, the guideline provides recommendations on how to tailor treatments to suit a woman’s individual symptoms, health history and preferences and how to assess which women could consider menopausal hormone therapy.

The guidelines were developed by a panel of six experts on the subjects and were chaired by Cynthia Stuenkel, MD. She is a founding member of The North American Menopause Society (NAMS) and also a clinical professor of medicine at the University of California, San Diego School of Medicine and an attending physician for the university’s Endocrinology and Metabolism Service.

“There is no need for a woman to suffer from years of debilitating menopausal symptoms, as a number of therapies, both hormonal and non-hormonal are now available,” said Cynthia A. Stuenkel, MD, in a press release .She also said that “Every woman should be full partners with her health care providers in choosing whether treatment is right for her and what treatment option best suits her needs. The decision should be based on available evidence regarding the treatment’s safety and effectiveness, as well as her individual risk profile and personal preferences.”

Women are eligible for HRT if they are younger than 60 years old and are no more than 10 years into menopause, Dr Stuenkel emphasized.

Before putting a patient on Menopausal Hormone Therapy (MHT), clinicians need to assess a patient's baseline risk for cardiovascular disease or breast cancer -- a high risk for either condition can constitute a contraindication to use of HRT.
Standard cardiovascular disease risk-assessment scores from organizations such as the American Heart Association has Standard cardiovascular disease risk-assessment scores for women who are at moderate or low risk for cardiovascular events; women falling into both of these categories can be considered for HRT.
 National Cancer Institute Breast Cancer Risk Assessment Tool is utilized by clinicians to calculate a woman's 5-year risk for invasive breast cancer, whereas the International Breast Intervention Study calculator predicts a woman's 10-year and lifetime risk.
The Updated guidelines specifically targets vasomotor symptoms (hot flushes/flashes/night sweats) and genitourinary tract symptoms (vaginal dryness or discharge, pain, burning or itching, urinary frequency, recurrent urinary tract infections).
Menopausal symptoms typically start a year before the last period and can be very bothersome for unpredictable time period; it could be as little as few months or 10-14 years after the last period.
"The most effective therapy [for both sets of symptoms] is HRT," Dr Stuenkel said.
"But we have listed many other nonhormonal and over-the-counter [OTC] options that physicians can use as well, and each of these options can be discussed with patients."
Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia.
These guidelines emphasize safety in identifying which late perimenopausal and recently postmenopausal women are candidates for various therapeutic agents.
Dr Stuenke advocates that women for HRT can receive estrogen replacement alone if they are without a uterus; if women have a uterus, they require the combination of estrogen plus progestogen to prevent endometrial hyperplasia and cancer.
Additional hormonal options for women with a uterus include estrogen combined with bazedoxifene and tibolone where available.
Women in the United States and some other countries have a broader range of therapeutic choices than ever before, including: MHT dose, type, and route of administration; new selective estrogen receptor modulators (SERMs) as solo or combination therapies; and expanded choices of nonhormonal prescription medications.
Other medical options recommended by the Endocrine Society include

• Transdermal estrogen therapy by patch, gel or spray is recommended for women who request menopausal hormone therapy and have an increased risk of venous thromboembolism – a disease that includes deep vein thrombosis.
• Progestogen treatment prevents uterine cancer in women taking estrogen for hot flash relief. For women who have undergone a hysterectomy, it is not necessary.
• If a woman on menopausal hormone therapy experiences persistent unscheduled vaginal bleeding, she should be evaluated to rule out endometrial cancer or hyperplasia.
• Medications called selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin or pregabalin are recommended for women who want medication to manage moderate to severe hot flashes, but either prefer not to take hormone therapy or have significant risk factors that make hormone therapy inadvisable.
• Low-dose vaginal estrogen therapy is recommended to treat women for genitourinary symptoms of menopause, such as burning and irritation of the genitalia, dryness, discomfort or pain with intercourse; and urinary urgency or recurrent infections. This treatment should only be used in women without a history of estrogen-dependent cancers.

Impact on quality of Life

The impact of severe menopausal symptoms on quality of life may be substantial," Dr Stuenkel noted.
In light of this, there are circumstances under which a woman with a history of coronary artery disease or even breast cancer might choose to accept a degree of risk that initially might outweigh the benefits of HRT.
Nevertheless, patients should be fully informed about the risks and benefits associated with HRT to enable them to make a decision that best balances these risk and benefits, Dr Stuenkel emphasized.
"We in the Endocrine Society were dismayed by the incredible drop-off in the use of HRT [following the Women's Health Initiative study]," she noted.
A 2012 Endocrine Society survey found that 72% of women currently experiencing menopausal symptoms had not received any treatment for them.
"And while we don't blame the average clinician for being confused or frustrated by all the contradictory data that have emerged over the past decade, we wanted to take a strong stance to simplify these data and to say that in carefully selected women, HRT will be the most effective therapy we have for menopausal symptoms," Dr Stuenkel added.
"So...the data we present in our guidelines help substantiate why HRT is a reasonable approach for carefully selected women, and physicians should be revisiting this question annually with their patients to discuss their decision regarding HRT and perhaps modify it if other health concerns have arisen in the preceding year."

Stopping the MHT

The guidelines also state that the approach to discontinuation of HRT is an individual choice, too.
Menopausal symptoms and joint pain can recur when HRT is discontinued, and depending on the severity of the symptoms, women may elect to restart HRT, perhaps at a lower dose, or seek relief with nonhormonal therapies.
"Anecdotally, some women find that a very low dose...maintains adequate symptom relief and well-being and prefer that to complete discontinuation," state the recommendations.
Resources for patients are available at www.menopausemap.org. The Hormone Health Network also offers a digital toolkit for healthcare providers.

Summary of Recommendations

·        The clinical symptoms, menstrual history, history of surgery (Hysterectomy with Bilateral oophorectomy) are sufficient to make the diagnosis of menopause for the majority of women. Laboratory studies are not a prerequisite for the diagnosis but may be used when necessary.

·        Menopausal Transition is also a good time for addressing other health issues   such as bone health, smoking cessation, alcohol use, cardiovascular risk assessment and management, and cancer screening and prevention.

·        For menopausal women < 60 years of age or < 10 years past menopause with bothersome VMS (with or without additional climacteric symptoms) who do not have contraindications or excess cardiovascular or breast cancer risks and are willing to take menopausal hormone therapy (MHT), the study suggest initiating estrogen therapy (ET) for those without a uterus and estrogen plus progestogen therapy (EPT) for those with a uterus.

·        Women at high risk for CVD, should receive nonhormonal therapies to alleviate bothersome VMS (with or without climacteric symptoms) over MHT.

·        Women at moderate risk  for CVD should  be started on transdermal estradiol as first-line treatment, alone for women without a uterus or combined with micronized progesterone(or another progestogen that does not adversely modify metabolic parameters) for women with a uterus, because these preparations have less untoward effect on blood pressure, triglycerides, and carbohydrate metabolism.

·        Non-oral estrogen is also preferred in the treatment of menopausal women with an elevated risk for venous thromboembolic disease. These patients should also receive a progestogen, such as progesterone or dydrogestone, which is more neutral in its effects on coagulation.

·        Women at high or intermediate risk of breast cancer considering MHT for menopausal symptom relief, the guideline suggest nonhormonal therapies over MHT to alleviate bothersome VMS.

·        The treatment plan should be reviewed annually, estimating the risk and benefits.

·        The taskforce also called on physicians to advise women about the uncertainty of over the counter medicines for menopause.

·        The study also  recommend informing women about the possible increased risk of breast cancer during and after discontinuing EPT and emphasizing the importance of adhering to age-appropriate breast cancer screening.

·        For young women with primary ovarian insufficiency (POI), premature or early menopause, without contraindications, we suggest taking MHT until the time of anticipated natural menopause, when the advisability of continuing MHT can be reassessed.

·        Stopping the MHT should be a shared decision-making approach to elicit individual preference about adopting a gradual taper vs abrupt discontinuation.

·        For women seeking pharmacological management for moderate to severe VMS for whom MHT is contraindicated, or who choose not to take MHT, we recommend selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) or gabapentin or pregabalin (if there are no contraindications).In  women not responding to these drugs  a trial of clonidine is suggested.

·        This new term “genitourinary syndrome of menopause” (GSM) combines the conditions of VVA and urinary tract dysfunction.

• Women with symptoms of vulvovaginal atrophy may be treated initially with a trial of vaginal moisturizers at least twice weekly. Low-dose vaginal estrogen therapy can be introduced if initial treatment is insufficient.
• Women with a history of endometrial or breast cancer may initiate treatment with vaginal estrogen therapy, but this decision-making process should involve the treating oncologist.
• Low-dose vaginal estrogen therapy does not require co-treatment with a progestogen.

·        Women with moderate to severe dyspareunia and vaginal atrophy may be offered a trial of ospemifene, which has been demonstrated to reduce dyspareunia and improve sexual satisfaction in randomized controlled trials.

·        Diabetes is considered by the AHA to be a CHD risk equivalent , which would suggest that women with diabetes should not take MHT. The evidence at this time is inadequate to make firm recommendations. An individualized approach to treating menopausal symptoms could be considered, with a low threshold to recommend nonhormonal therapies, particularly in women with concurrent CVD.

The Hormone Health Network, the Endocrine Society’s public education arm, developed an interactive digital resource called the Menopause Map^TM for women to explore the stages of menopause and learn about symptoms they may experience. The Menopause Map^TM related resources are available at
http://www.hormone.org/menopausemap/postmenopause.html

The Hormone Health Network also offers a digital toolkit for health care providers.

References :
http://press.endocrine.org/doi/citedby/10.1210/jc.2015-2236
http://www.medscape.org/viewarticle/853793
https://www.endocrine.org/membership/email-newsletters/endocrine-insider/2015/october-16-2015#/9
http://menopausehealthmatters.com/hormone-replacement-therapy/
http://answers.webmd.com/expert/39928/cynthia-stuenkel-north-american-menopause-society
https://www.endocrine.org/news-room/current-press-releases/experts-recommend-assessing-individual-benefits-risks-of-menopausal-therapies