It’s raining men(opause)

Hi everyone,

Menopause is a hot topic lately, with Oprah hosting town halls with celebrities on the topic in addition to a slew of new menopause startups having just raised $530M in the past few years. Andropause isn’t far behind – testosterone startups like Hone Health, Ro and others are also on the rise, lifted by the tailwinds of consumer trends in longevity and performance thanks to doctors like Attia and Huberman.

At Parsley, where we have been prescribing hormone replacement therapy (HRT) to men and women since 2016, we are seeing more demand for hormones than ever. I prescribed HRT twice last week to two female patients now in menopause, both 51 – the age at which menopause starts on average in the US – and found myself having a much different conversation with them than when I first saw them eight years ago. Not only were both inquiring about starting hormone therapy, both had researched their options, had detailed questions on the merits of bioidenticals vs synthetic, whether estriol was needed alongside estrogen or not, and whether they should start testosterone too. They sounded… excited.

I thought to myself, wow, the stigma is gone. Eight years ago my patients approached HRT with trepidation, fear, and what felt like a level of guilt, as though they were considering risking their lives for the sake of managing a few pesky hot flashes and night sweats.

Thankfully, no more. That mindset is outdated. HRT, it turns out, is highly beneficial not just for managing symptoms, but potentially for preventing chronic disease.

The three myths of HRT in women:

Myth 1: HRT causes breast cancer. This is not true. In fact the Women’s Health Initiative (WHI) study in 2002, which originally caused all the controversy, actually showed lower all-cause mortality in those who started estrogen in mid-life, mean age 47. The study did show a very slight increase in the incidence of breast cancer (1 additional case per 1000 women) in a group of women who had used HRT before the study in addition to during the study, but no increased incidence in another group of women who had not used prior HRT.

Furthermore, the study, which followed women for 20 years, showed no increased breast cancer mortality from taking HRT. In fact, the group that took estrogen only (as opposed to estrogen + a synthetic form of progesterone no longer in use called MPA) had a 40% lower overall mortality than the other group.

The TLDR here is that the study doesn’t link estrogen replacement to breast cancer, and that if anything it could be protective, and yet this message was picked up by the press and led to decades of underprescribing HRT to millions who could have benefitted from it.

There is a lot more here to dive into – the ways in which HRT has evolved over time much like the birth control pill, and the fact that the research seems to show that starting HRT over 10 years after menopause does seem to increase risk while not providing any benefit. But we can go deeper in another post.

Myth 2: HRT causes increased risk of dementia. In fact, the opposite is true, when taken in mid-life (mean age 47) around the time of menopause, HRT has a protective effect. Per one large study, risk was only higher in a group that did not take HRT around menopause but started estrogen later in life (mean age 76). The conclusion here is, again, that starting HRT later in life (greater than 10 years post menopause), may have greater risk. But the risk for those who started in mid-life and continued was equivalent to those who started in mid-life and stopped.

Myth 3. HRT causes heart disease. This is also not true. An analysis done later of the women’s health data showed that for those starting HRT within 10 years of menopause, HRT may have been protective against heart disease; for those starting between 10 years and 20 years out from menopause, HRT was neutral to cardiovascular outcomes and for those starting 20 years post menopause, it was associated with slightly worse cardiovascular outcomes. In addition the form of estrogen studied was CEE, an oral estrogen that was associated with slightly higher blood thickness and therefore clot risk, but this form of estrogen is no longer used.

At Parsley we prescribe transdermal estrogen in newer forms which have not been shown to have any clot risk. What is not known is if HRT is truly protective for heart disease: some research is positive, some is ambiguous. We know more research is needed, but we can say that HRT does not independently worsen risk of heart disease absent other factors.

Lastly, HRT has been shown to be protective against osteoporosis. When estrogen drops off in menopause, bone density drops off too. Taking estrogen plus progesterone has been shown to preserve bone density, though the impact fades as soon as you stop taking hormones.

Who should not take HRT?

For women: According to ACOG (The American College of Obstetrics and Gynecologists), anyone who has a history of breast cancer or endometrial cancer, a history of blood clots or stroke, or liver disease, should not take HRT.

For men: Testosterone therapy that starts too early can lead to infertility; plus, there is mixed research on testosterone’s impact on heart disease. In all cases, HRT should be monitored through regular testing and visits with your HRT-literate provider who can monitor for side effects, overall levels and order preventive screening as necessary.

How long can you take HRT?

The simple answer is we don’t know. Longitudinal trials of HRT, including bioidentical HRT, which means hormones sourced from animals that more closely mimic human hormones, vs the synthetic hormones that have been used in studies, may not be done any time soon. We simply don’t have sufficient data on what it means to start hormones in mid-life and continue them for 30+ years. As a result, ACOG recommends stopping HRT once symptoms of menopause have subsided. But I have to wonder if this recommendation is dated too? With all the preventive benefits of hormones, in 5 or 10 years will we be recommending everyone take them for decades? It’s definitely possible.

What we do know however is that per the data we have, starting HRT late in life, more than 10 years after menopause, seems to come with slightly increased risks of dementia, heart disease and breast cancer, while starting in mid-life appears to be neutral to beneficial.

We also know that surveillance and screening while on HRT is important. At Parsley, we monitor heart health through tests like hsCrp, ApoB, Lpa, and homocysteine. We also encourage regular mammogram and self breast exams (on or off of HRT) and paying attention to symptoms; for example, ongoing spotting in a postmenopausal woman can be a side-effect of improperly titrated HRT, but can also be a sign of endometrial cancer.

If it were me?

I always get asked, what will I do in the future when it comes to hormones? Of course, something could change in the data or my own health to change this, but as of today, based on what we know, I will likely plan to take HRT proactively. I most likely will take either compounded bioidentical estrogen cream (my preference) or a synthetic estrogen patch, oral progesterone, and if my natural testosterone levels fall, I will consider testosterone replacement too. By the way, for a future post, some women maintain their testosterone levels post-menopause, and when I see this I don’t replace it because it’s there and not missing!


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