New Menopause Guidelines Update HT Safety Evidence

Tara Haelle

August 18, 2016

Hormone therapy (HT) continues to be the most effective treatment for menopause symptoms such as vasomotor symptoms and urogenital atrophy, according to updated guidelines on managing women's overall midlife health from the International Menopause Society.

Because the risk–benefit ratio differs for perimenopausal women compared with older, postmenopausal women, "[Menopausal HT (MHT)] must be individualized and tailored according to symptoms and the need for prevention, as well as personal and family history, results of relevant investigations, the woman's preferences and expectations," write Rodney J. Baber, MD, from the University of Sydney in Australia, and colleagues from the International Menopause Society Writing Group.

"Consideration of MHT should be part of an overall strategy including lifestyle recommendations regarding diet, exercise, smoking cessation and safe levels of alcohol consumption for maintaining the health of peri- and postmenopausal women," the authors write.

The recommendations appeared in Climacteric, along with a revised consensus statement on HT. Various major menopause and endocrine medical societies, including the North American Menopause Society and the Endocrine Society, endorse the consensus statement.

"The revised statement contains only areas of consensus and does not replace the more detailed and fully referenced recommendations of the individual societies," write Tobie de Villiers, MBChB, from the University of Stellenbosch in Cape Town, South Africa, and colleagues in the consensus statement on HT.

The recommendations update the previous ones issued in 2013, but with several new features: grades for the recommendations, levels of evidence, and "good practice points."

The recommendations open with a discussion of the contributing factors and subsequent effects of weight gain and obesity, pointing out the lack of evidence for hormonal changes contributing to weight gain, along with an overview of physiological changes in women at midlife.

Benefits Outweigh Risks

In addition to clarifying the most recent evidence on risks from HT, the recommendations discuss other benefits of HT in prevention of various diseases of aging. "Increasing data indicate benefits for primary prevention of osteoporotic fractures and coronary artery disease and a reduction in all-cause mortality for women who initiate MHT around the time of menopause," the authors note.

"New data and re-analyses of older studies by women's age show that, for most women, the potential benefits of MHT given for a clear indication are many and the risks are few when initiated within a few years of menopause."

The findings appear thorough and effectively clarify the evidence surrounding HT as much as is possible, Gretchen Makai, MD, director of minimally invasive gynecologic surgery for the Department of Obstetrics and Gynecology, Christiana Care Health System, Wilmington, Delaware, told Medscape Medical News.

"These recommendations give enough evidence to almost give providers 'permission' to recommend [HT] to help women who are suffering because many practitioners have been hesitant," Dr Makai explained. "The evidence for HT is so broad, and the way it affects women is so vast, that it's really difficult for a provider who is evidence-based, but not at a major academic center, to keep up with the guidelines."

Additional Evidence Regarding Risks for Cancer, Heart Disease

Among the most helpful aspects of the new guidelines are the more precise numbers for cancer risk with HT, Dr Makai said. "The numbers they gave us for breast cancer will change the way I counsel women. I used to say it's very low, but it's not zero, but I can give a number now."

The guidelines cite the increased risk for breast cancer attributable to HT as less than 1 per 1000 women per year of use, which is a risk similar to or lower than the contribution of factors such as a sedentary lifestyle, obesity, and alcohol consumption.

"It is intriguing that in the [Women’s Health Initiative (WHI)] trial, there was no increased risk in breast cancer in the estrogen-only arm. This raises questions about the role of progestogens in breast cancer," Paula Amato, MD, associate professor, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, told Medscape Medical News. "Although, no conclusions can be drawn from WHI regarding progestogens and breast cancer because the populations in the two arms of the trial were sufficiently different, making comparisons difficult."

Another area of contention the recommendations addressed is the association between HT and various heart risks, although the evidence still appears limited.

"The most controversial issue regarding HT in my opinion is whether HT is beneficial for preventing heart disease when started early; ie, before age 60 and within 10 years [of] menopause," Dr Amato said. "WHI showed that it is clearly not beneficial, and in fact may be harmful, when started later. The preponderance of the evidence seems to suggest a protective effect when started early. But, this has not been definitely proven in large, long-term, [randomized controlled trials]."

Similarly, Dr Amato pointed out, more research is needed to understand the potential effects of transdermal estrogen. "There is also some suggestion that transdermal estrogen may be safer than oral with respect to stroke and thromboembolic risk. But, this is based on surrogate markers, and we are still lacking long term outcome data."

The recommendations can help practitioners stratify their patients' risk, which is something an app would be particularly helpful with, Dr Makai said. She would like to see more information about managing obese women with vasomotor symptoms, particularly as evidence suggests these women have more frequent hot flashes.

"They are already at higher risk for pulmonary embolism, but they're more in need of HT for their greater symptoms," Dr Makai pointed out, adding that their obesity also increases their risk for breast cancer. She was surprised, however, to see discussions about testosterone therapy for sexual dysfunction, as this is not available in the United States.

Also among the updates to the recommendations is a new definition for vulvovaginal atrophy, now called genitourinary syndrome of menopause "to describe more accurately the constellation of urogenital symptoms and signs associated with menopause and to remove the negative stigma of atrophy," the authors write.

The recommendations paper writing was funded by the International Menopause Society. Coauthors reported various financial relationships with Abbott, AbbVie, Acerus Pharmaceuticals, Actavis, Adcock Ingram Ltd, Allergen, Amgen, Astellas, Bayer, Besins, BMR, Colin Health, Cook ObGyn, Ferring, Gideon Richter, Isdin, JDS Therapeutics, Lawley Pharmaceuticals, Merck, Mylan, Noven, Novo Nordisk, Pfizer, Philips Ultrasound, Pierre Fabre, Radius Health Inc., Roche Pharmaceuticals, Sermonix Pharmaceuticals, Shinogi, TEVA Women's Health Inc, and Therapeutics MD.

Climacteric. 2016;19:109-150. Recommendations abstract. Published online June 20, 2016. Consensus statement extract

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