Primary Care Corner with Geoffrey Modest MD: Menopause Symptom Treatment

By Dr. Geoffrey Modest

There was an intriguing editorial written by JoAnn Manson and Andrew Kaunitz suggesting that the pendulum has swung too far, and that too few women are receiving hormone therapy for menopausal symptoms (see N Engl J Med 2016: 374; 803).

Their points:

• We are an aging population: by 2020 there will be >50 million US women >51 yo (mean age of menopause)
• 75% have symptoms of menopause; women with moderate-to-severe symptoms often have them for more than 10 years. Symptoms include poor sleep, mood changes, difficulty concentrating and impairment of short-term memory.
• The most effective therapy for moderate-to-severe symptoms is hormone therapy.
• Overall, about 20% of women have such severe symptoms, have no contraindication to hormone therapy (e.g. excessive risk of breast cancer/cardiovascular disease; and I would add thrombotic events, active liver disease, stroke, and, to be safe, any thrombophilic disorder), and most remain undertreated
• Background here: in the past huge numbers of women received hormone replacement therapy in an attempt to decrease cardiovascular events/mortality and preserve bone strength, until the Women’s Health Initiative found increased cardiovascular mortality in its initial report in 2002. This lead to an 80% decrease in hormone prescribing [I would add that at that time we were also getting better, well-tolerated meds for these issues: statins and bisphosphonates, which seemed a much more reasonable and well-studied approach]
• But the WHI looked at long-term therapy in older women (mean age 63), and may have little relevance to women in their 40s-50s on shorter courses of therapy for these distressing and sometimes functionally-impairing symptoms
• One consequence of our not treating menopausal symptoms well is the proliferation of non-regulated compounded hormone products (a recent survey found that 35% of current hormone users are on these products)
• But hormone therapy is really well-studied, with:
  • Much lower risk of adverse events in those in their 50s vs older, including, in events per 1000 women over 5 years (the data is significantly better for those on conjugated equine estrogens CEE alone vs with medroxyprogesterone MPA):
  • Death from any cause: -5.5 (i.e. benefit) in those on CEE vs -5.0 on CEE/MPA
  • ​Fractures: -8.0 with CEE vs -12.0 for CEE/MPA [though actually hip fractures may be worse with CEE but better with CEE/MPA]
  • All cancers: -4.0 with CEE vs -0.5 for CEE/MPA
  • Diabetes: -13.0 with CEE vs -5.5 for CEE/MPA​
  • Coronary heart disease: -5.5 with CEE vs +5 for CEE/MPA
  • Deep venous thrombosis: +5 with CEE vs +5.0 for CEE/MPA
  • Breast cancer: -2.5 with CEE vs +0 for CEE/MPA [the decreased risk of breast cancer in those on just CEE was found in the Women’ Health Initiative]
• The data are reasonably robust that transdermal estrogens are even safer [bypass the first-pass hepatic metabolism of oral meds, with documented decreases in vitamin K-dependent clotting factor induction, and observational data of many fewer DVTs; also oral estrogens more associated with high triglycerides and CRP levels]
• Also undertreated is vulvovaginal atrophy, occurs in 45% of women, adversely affects physical and sexual health/quality of life, and responds well to topical vaginal estrogens
• And there is a concern that new physicians are not receiving training in prescribing hormones, as verified in studies showing that 3/4 of internal medicine residents understand the importance of treating menopausal symptoms, yet 3/4 felt they did not get adequate training

A few comments:

• Although I do prescribe medications for disconcerting menopausal symptoms, I usually will suggest to the patient trying nonhormonal meds first (e.g. SSRIs, SNRIs, clonidine, gabapentin, the data on herbal medicines is pretty mixed, as are the data for exercise. Weight loss can help. I have prescribed mostly venlafaxine but it seems that pretty much all SSRIs and SNRIs work). But the vast majority with severe symptoms do require estrogens. Almost always, I suggest transdermal estrogens, for reasons noted above, and typically have had great success with that.
• Women with intact uteri should have a progestin prescribed, since endometrial hyperplasia can happen within months of starting estrogens. Though not great data for this, I tend to prescribe micronized progesterone (as opposed to MPA, micronized progesterone does not decrease HDL levels). Aome people do well with progesterone-secreting IUDs, though there is some (probably minimal concern) that increased blood levels of progesterone can occur and one observational study did find a higher breast cancer incidence. I have not prescribed this so far, but it sounds pretty good to me…
• Also, my experience is that most women spontaneously stop the therapy within a couple of years, though some have recurrent symptoms (tapering the dose sometimes works)
• So, the risk of hormone therapy is really very low in young, healthy women taking these meds for 5 years. I share the editorialists concerns that we are probably undertreating a condition which really affects women’s lives/functioning, and that we are not adequately training residents/new physicians in feeling comfortable with well-researched therapies.

For more detail on menopause treatment studies and other recommendations, see practice guidelines by the Endocrine Society:  J Clin Endocrinol Metab 100: 3975)

See blog https://stg-blogs.bmj.com/bmjebmspotlight/2015/02/21/primary-care-corner-with-geoffrey-modest-md-length-of-menopausal-symptoms/​ which noted that 20% of women have menopausal vasomotor symptoms 13 years post-menopause, much longer than noted in many published guidelines.