Tuesday, 19 September 2017

#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.

11 comments:

  1. Thanks for this. This is a very important issue and needs to be addressed at a national level. I had no idea you were feminist.

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    1. How can I not be a feminist with two daughters; I care about their future. I am also married to a modern day suffragette; my wife cares passionately about women's issues.

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    2. Didn't the NHS issue a directive to doctors recently to listen to their women patients more ;)

      https://www.theguardian.com/society/2017/sep/06/listen-to-women-uk-doctors-issued-with-first-guidance-on-endometriosis

      thank you for the helpful entry.

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  2. At first, I was relieved that post menopausal Hormone replacement therapy HRT may not be good for me. After reading this and considering my insomnia, etc, I will talk with my Doctor. To be honest, I'd rather go buy some today. Make it legal 😎🤔

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  3. I posted a question on the unrelated blogger site a couple of months ago about HRT and got no response from anyone! Bit frustrating! As Ms mostly affects women I would have thought that the menopause would be a frequently discussed issue, but obviously not. My neurologist who I have seen for 10 years seems to have no opinion on the menopause and MS and I have to say I do wonder if because the majority of neurologists are men and that, because the menopause is often considered something women should just get on with it gets seriously overlooked with regards to its effects, which can be severe on the healthiest of women

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  4. Thanks for this post. I hope it benefits many women.
    I've been on HRT since 2011, some four years before being diagnosed with MS. Researching at the time I was convinced that, since the scares in around 2002, the evidence was overwhelmingly that HRT presents minimal risk, especially in relation to the benefits. I distinctly recall reading from the International Conference on the Menopause that year that countries such as the UK where behind the times in the position being adopted by the health care service. Luckily I've a supportive GP and neurologist. If other women can face taking on this battle I'd recommend a general search on google for scientific research on the menopause- be prepared for heaps of studies and repeated conclusions that it really is quite safe! I know many women don't wish to take it, but for those that do - best wishes with tackling any difficulties in getting it prescribed.

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  5. Thank you so much for this and all you do. My MS was finally diagnosed when I hit Menopause and went down hill. My Gyno very proactive and helped me get Estriol I read about in trial for women with MS. Don't know if helping or not, but not killing me. I don't leave my name as I am still trying to work and keep insurance. Not easy.

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    1. My partner's MS was diagnosed after she was put into induced menopause for 5 years due to an estrogen fed breast cancer).


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    2. That's interesting as all the evidence suggests that oestrogen is neuroprotective, so the induced menopause may have aggravated underlying MS but I'm just speculating here.

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    3. yes, we have always wondered about that. we suspect we won't ever know for sure but, having had her estrogen return after the 5 years of induced menopause, we are not looking forward to her natural menopause.

      A lot of what in hindsight could have been MS symptoms were at the time put to cancer treatment side effects. she was diagnosed after she finished 'induced menopause' (about 2 years or so afterwards) - which would, according to one of barts' theories, would be when she would really be feeling the symptoms of damage created while her estrogen was suppressed.

      ahhh all the ifs and maybes...

      Feel like she is between a rock and a hard place in respect of HRT though still need to speak to her oncologists about it.

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    4. I'm intrigued by this question of hormones and MS.

      In a social networking group that participates many women who use oral or injectable contraceptives appear to have more relapses than those who use other contraceptive methods, such as barrier (copper IUDs, condoms, etc.).

      And the fact that MS in men is more active or already progressive from the beginning.

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