#ClinicSpeak: post-menopausal hormone replacement therapy in women with MS

HRT has shown not increase mortality in postmenopausal women. #ClinicSpeak #WomenPower #BrainHealth

Summary: A long-term, follow-up, study of hormone replacement therapy in post-menopausal women shows that HRT does not increase mortality (death). If your GP has refused you HRT in the past based on the assumption that HRT is unsafe you can now challenge this position armed with this new data. 

There is a reasonable scientific rationale why women with MS who are post-menopausal should consider hormone replacement therapy (HRT). It helps with bone health, a well-defined problem in MS, and HRT is possibly neuroprotective. In addition, HRT addresses troubling menopausal symptoms that may, or may not, exacerbate MS-related symptoms. These include mood disorders, poor sleep, fatigue, low libido and weight gain. Over the last few years, there has been an increasing trend for GPs (general practitioners or family doctors) to refuse HRT to several of my patients based on the fact that it increases your risk of cardiovascular events and breast cancer, albeit by a very small amount. Despite several of my patients stating that they are prepared to take these risks their GPs have refused to prescribe them HRT. It is clear that paternalistic medicine is alive and kicking. 

The following paper on all-cause mortality shows that among postmenopausal women HRT for ~ 6-7 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. If you are brave and feel like taking on your GP you can now go armed with this information back to your GP and demand them to reconsider their previous decision. 

I also want to state that a lot of GPs view HRT as being a lifestyle therapy, which is one of the reasons why they are so reluctant to prescribe it. In short, HRT is an anti-aging drug and a lot of women take HRT to fight back the ravages of aging. So what, if that is the reason why women want HRT who am I, or their GPs, to say no? I now think there is a very strong case for HRT becoming available as an over-the-counter (OTC) medication so that women can make their own decisions about their health. What do you think? 

Manson et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-SpecificMortality: The Women's Health Initiative Randomized Trials. JAMA. 2017 Sep 12;318(10):927-938.

IMPORTANCE: Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.

OBJECTIVE: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.

DESIGN, SETTING, AND PARTICIPANTS: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.

INTERVENTIONS: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).

MAIN OUTCOMES AND MEASURES: All-cause mortality (primary outcome) and cause-specific mortality(cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.

RESULTS: Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality 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; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-causemortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.

CONCLUSIONS AND RELEVANCE: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

CoI: none in relation to this post.

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