New Findings on Hormone Therapy

Hormone Therapy

Researchers continue to assess the effects, good and bad, of hormone therapy (HT) used to treat menopause symptoms, notably hot flashes and night sweats. HT involves the use of estrogen plus progesterone in women who have a uterus, and estrogen alone in women who have had a hysterectomy. Here’s a look at three recent studies.

Hormone therapy and knee osteoarthritis

Hormone therapy may reduce the risk of knee osteoarthritis (OA), according to an observational study in Menopause that involved nearly 4,800 postmenopausal women over age 50 in South Korea. Women on HT for a year or more were about one-third less likely to have this disorder than those not on hormones. Menopause is associated with increases in OA, presumably due to the hormonal changes that occur then—in particular, decreasing estrogen levels. Estrogen supplementation may slow cartilage damage through anti-inflammatory effects, the researchers noted. Plus, estrogen may help control musculoskeletal pain by inhibiting pain pathways in the spinal cord.

The study does not prove a cause-effect relationship between HT and reduced knee OA, however, and because it included only Korean women, the findings may not apply to other ethnic or racial groups. Thus, the findings do not warrant starting HT for any possible joint-health benefits.

Hormone therapy and blood clots

Oral hormone therapy increases the risk of rare but potentially fatal blood clots (venous thromboembolism, or VTE), a study from the U.K. in BMJ confirmed—but transdermal delivery (patches, gels, creams) does not. Using 18 years of data from more than 470,000 women ages 40 to 79, the researchers found that those taking hormone pills had a 12 to 138 percent greater risk of VTE than those not on HT, depending on the formula (estrogen only or combined with progesterone), while those treated orally had about a 70 percent greater risk than those treated transdermally. And conjugated equine estrogen (from horse urine) was riskier than synthetic estrogen.

Overall there were nine extra cases of VTE per 10,000 women on oral hormones per year. No increased risk was seen for transdermal hormone use, possibly because of the way the drug is metabolized in the body, compared to oral medications. (By bypassing the gastrointestinal tract and liver, transdermal delivery has fewer undesirable physiological side effects and greater bioavailability.)

Like the knee OA study, this one was observational and thus also does not prove cause and effect. And the background risk of VTE is low—about 2 to 4 cases per 10,000 people per year. Still, the findings back a 2017 joint recommendation from the American Association of Clinical Endocrinologists and the American College of Endocrinology to use transdermal formulations instead of oral estrogen to reduce the risk of blood clots.

Previous research has also linked HT to VTE, but this new study provides a more detailed look at the relative risks of different forms of HT, which could help in making better treatment decisions, especially for women already at higher risk for VTE due to obesity or other factors.

Vaginal estrogen safety

Low-dose vaginal estrogen (in creams, tablets, suppositories, or an estradiol ring) is prescribed for the genital and urinary symptoms of menopause, such as vaginal dryness, pain during intercourse, urinary urgency, and recurrent urinary tract infections. It appears to be safe, according to another observational study in Menopause, which followed women in the Nurses’ Health Study over 18 years. The study—which included nearly 900 women who were on vaginal estrogen and about 53,000 who were not—found no increased risk of heart attacks, strokes, blood clots, or cancer (ovarian, endometrial, colorectal, or invasive breast) in users versus non-users. That’s because, unlike oral and transdermal hormone therapy, vaginal estrogen, which is formulated for local effects, has minimal systemic absorption. (This means, however, that it doesn’t treat hot flashes.)

An analysis of data from the Women’s Health Initiative Observational Study, published in 2017, also found vaginal estrogen safe, and the North American Menopause Society and other health organizations recommend it over systemic HT for treating menopause-related genital and urinary symptoms. Women with breast cancer should consult their oncologists before using it, though, because there’s still a risk of small increases in circulating estrogens.

Bottom line: Despite a spate of re­­cent studies that have largely been encouraging in terms of the safety of HT, many women—and their doctors—remain wary of using hormones to treat menopause symptoms. If you are bothered by hot flashes and other symptoms, talk to your doctor about whether you are a candidate for this treatment. You and your doctor should weigh your risks and benefits based on such factors as your age, medical history, and severity of symptoms. Nonhormonal treatments are also available and should be considered first.