An OB Gyn's view of the menopause market

This piece was written by obstetrician gynecologist Dr. Barbara Levy, with support from our new women’s health editor Leslie Schrock. Schrock is also the author of the brilliant women’s health newsletter Fertility Rules.

Menopause is one of the hottest growth areas in healthcare, with more than $500 million in venture capital funding flowing into the sector since 2015, plus many headlines about the gap in care. But the path to the front page hasn’t been easy.

Nor has the path to getting women effective treatment. Hormone replacement therapy (HRT) - or as it is also known, menopause hormone therapy (MHT) - has a fraught history of flawed research and misinformation. Making matters worse, we don’t have sufficient numbers of trained menopause providers to take care of patients who need help. All of that has led to the explosion of companies that prescribe HRTs via telemedicine, but do little else to support women through this transitional time.

As an OB-Gyn, who’s been watching this market carefully for years now, I’d argue that we’re at the very beginning when it comes to addressing the needs of women experiencing menopause. There’s a wide variety when it comes to quality. And there’s still far more work to do.

But first, a little history.

The Rise of HRT

Estrogen was first discovered by researchers Edgar Allen and Edward Adelbert Doisy in 1923. A few decades later, in 1941, estrogen was approved for the treatment of menopausal symptoms, including hot flashes, night sweats, brain fog, painful sex. Until that point, there was no proven treatment. Estrogen hit an inflection point after Dr. Robert Wilson published the book Feminine Forever (sponsored by the pharma giant Wyeth-Ayerst) in the 1960s, positioning it as the fountain of youth. This widespread enthusiasm lasted until the 1970s, when studies demonstrated an association between estrogen-only treatment and overgrowth of the uterine lining and uterine cancer.  

Soon after, scientists reported that adding a derivative of the natural ovarian hormone progesterone could prevent the development of uterine cancer in women using estrogen. Prescriptions for HRTs that combined estrogen and progesterone soared.

The NIH’s Women’s Health Initiative Study (and its fallout)

The research on estrogen didn’t stop there. Epidemiologists were intrigued by the health differences among women who chose to use hormones for menopausal symptoms versus those who did not. Conflicting data from several large studies showed what appeared to be a clear relationship between estrogen therapy and a significant reduction in heart disease risk and mortality.  

This finding and the rising incidence of heart disease in the U.S. led the National Institutes of Health (NIH) to sponsor a very large (and expensive–recruiting the 100,000+ women required for the study cost over $600 million) randomized controlled trial of menopausal hormone therapy.

The resulting Women’s Health Initiative Study (WHI) was meant to answer the question: 

Should every menopausal woman be placed on hormone therapy to prevent heart disease?

Unfortunately, the WHI’s study design turned out to be deeply flawed, and the after-effects of its findings still haunt women to this day. The problems with the study included:

1. Only older women were recruited so that there would be sufficient incidence of heart disease to see a statistically significant difference. 

2. The study population was also limited to women without menopause symptoms so both the patients and their physicians could be “blinded” to treatment (estrogen is so effective at treating menopausal symptoms that if people had symptoms, everyone would know immediately whether they were on the active treatment or placebo.) 

3. The study used the most widely prescribed medications at the time (late 1990s) but failed to include other options, like estradiol, which is natural to humans, or delivery mechanisms like hormone patches, creams, or pellets.

The trial was stopped early due to a perceived signal that treatment with estrogen and progestin increased the risk of breast cancer. The 20-year findings since then have found that this observation (and the lack of benefit relative to heart disease) was incorrect. 

As a physician, I still have PTSD from watching the NIH press conference in July 2002, where it was implied that these hormones were dangerous.  Prescriptions plummeted by 78% almost overnight — and my office phone rang off the hook for weeks as patients were told to stop taking their hormones. When the hormones stopped, menopausal symptoms returned with a vengeance.

In subsequent years, symptoms related to the transition to menopause, a process that can take up to 10 years, have been dismissed by traditional medical professionals. I am not proud of how my peers in medicine have treated women (editors’ note: here’s a brilliant new book on that topic if you’re curious to learn more.) Fear-mongering on social media and elsewhere has displaced science and healthcare professionals, and women are still desperate to find non-hormonal interventions to address symptoms.

Let me be clear: While menopause is a “natural” process, its symptoms are, for many women, completely debilitating. The notion that hormone treatment is dangerous has led some women to believe they should just tough it out or seek out unproven treatments. This deeply concerns me. Women should not have to suffer like this in silence.

What we know today about HRT

22 years after the publication of the WHI, we know more about treatments, hormones, non-hormonal options, and supplements. Here’s a summary that I share with my patients as we discuss their treatment options. I hope you find it helpful should you ever need to share it:

• All hormones are not created equal: Premarin, the drug used in the WHI, has significantly different effects than the estrogen naturally produced by the ovary, estradiol. Provera, the progestin in the WHI, also has different effects than natural progesterone

• HRTs reduce all-cause deaths without an uptick in breast cancer or brain clots:  The Danish Osteoporosis Study (DOPS), initiated in 1990, was a randomized trial like the WHI but enrolled women at the time of menopause and treated them with estradiol and progestin (when necessary) for 10 years. Unfortunately, the study was terminated prematurely when the results of the WHI were published in 2002. However, the follow-up showed no increase in breast cancer or blood clots and a whopping 50% reduction in death from all causes, including a 30% reduction in heart disease. These outcomes were not widely publicized.

• Timing matters:  Starting hormones during perimenopause is different from starting them 10+ years after menopause. The average age of menopause is 51, but the average age for women enrolled in the WHI was 63, 10 years after menopause. Long-term studies have validated that starting hormones when symptoms develop and using estradiol with or without progesterone results not only in a significant improvement in menopausal symptoms and quality of life but also other positive long-term health outcomes, including preservation of bone density and a reduction in cardiovascular disease and death.  

• Estrogen does not cause breast cancer: And menopausal hormones do not worsen the outcome of breast cancer in those who are diagnosed. Estrogen significantly reduces the incidence of and mortality from breast cancer.  The WHI 20-year follow-up showed a 22% reduction in breast cancer incidence among women taking Premarin and a 40% reduction in death from breast cancer among those who got cancer while taking the hormone.

The big business of menopause

Not all hormones are created equal, nor are all venture-backed companies. So here’s one provider’s perspective on what I’m seeing in the market today. 

Despite all the progress, I believe the public and medicine are still hopelessly stuck in 2002, and millions of suffering women are still left frightened, confused, and desperately searching for what they may consider “safer” alternatives. One example: New, expensive non-hormonal pharmaceutical alternatives to treat vasomotor symptoms—hot flashes and night sweats—are available, but they do not offer the preventive benefits of estrogen. (GoodRx shows a monthly cost of $570-$615/mo in my area).

Moreover, I’m skeptical of supplements. People think of supplements and nutraceuticals as non-drug alternatives. But these are drugs without the benefit of randomized controlled trials and FDA approval to demonstrate safety and effectiveness. The placebo effect is huge, so many supplement enthusiasts become true believers in whatever alternative therapy they’re using.  In addition, over the years some supplements have been proven harmful to patients.

Finally, I see new entrants creating information asymmetries.

The lack of adequate training in hormones by many primary care providers and Ob-GYNs has created a significant opportunity for menopause-specific care delivery businesses, which don’t integrate with the patient’s ob-gyn or primary care doctor. I’m personally concerned by that trend, although I acknowledge that it’s better than no treatment at all.

A challenge for these companies' patients is that not all symptoms are related to declining hormone levels during perimenopause or menopause. They may be experiencing thyroid problems or blood sugar fluctuations causing their symptoms. In an ideal world, the management of menopause symptoms should be integrated into the care for all other conditions a woman may suffer from.

Healthcare professionals can best treat patients when they know about every treatment a woman is taking. What I see instead is the rise of companies that do not have licensed practitioners available to patients who can diagnose other medical conditions and prescribe medication and order labs. This has been a problem in my practice. There’s also been a move towards “Pill Mill” behavior, with the rise of companies creating pharmacies and selling medications directly to patients alongside supplements — all without adequate clinical support.

Women deserve better. After decades of paternalism and symptoms getting ignored, we’re finally in a moment where menopause is getting real attention and resources - although I will be the first to stress that it’s only a drop in the bucket. As an industry, let’s not waste the moment.

Where do you stand on all these new menopause treatments? We’d love to hear from you at [email protected].

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