Could testosterone be a useful treatment for menopause?

The world may be getting over the idea that men are from Mars and women from Venus, but public perception still holds that testosterone is the male hormone, and estrogen, the female. That can make the following fact a little puzzling: There is more testosterone than estrogen in a premenopausal woman’s body.

Testosterone levels decrease with time and reach especially low values after menopause, which can lead to loss of bone density, lower energy, and depression. Some doctors prescribe testosterone as a potential source of relief for such symptoms, though there isn’t a testosterone product approved by the Food and Drug Administration for female use.

There’s disagreement within the medical community about whether testosterone treatments should go mainstream, or if it’s an option that would help very few. And even as hormonal treatment for menopause becomes more popular, the absence of a substantial body of research on the effects of testosterone in menopausal women means that both doctors and patients are still frequently in the dark about its potential benefits and safety.

“I think one of the big barriers is not knowing that testosterone is for all bodies,” said Kelly Casperson, a urologist and menopause specialist who treats postmenopausal patients with testosterone. “We gender hormones. We say estrogen is for women and testosterone for men. And it’s so narrow-minded and it’s so limiting … If that’s where we’re starting, of course we can’t normalize testosterone for female bodies.”

A dearth of data on testosterone treatment for women

There are some crucial differences in how estrogen and testosterone work in women’s bodies. Estrogen fluctuates during the menstrual cycle, but it’s produced consistently by the ovaries and adrenal glands until menopause. Then its production decreases quite dramatically, causing a wide range of symptoms that are debilitating for many women, such as hot flashes, mental health issues, and sleep problems. Women’s testosterone levels, on the other hand, peak when they are in their teens and 20s. They go down gradually afterward, without a similarly drastic drop.

Because testosterone levels vary considerably from one woman to another, doctors seldom prescribe the hormone to women until they’ve gone through menopause, at which point a deficiency in the hormone is easier to detect. For decades, it has been prescribed to treat hypoactive sexual desire disorder (HSDD), a loss of sexual desire that affects an estimated 10% of women across all age groups, and women who take testosterone during menopause also report more energy, lower levels of depression, and increased muscle mass.

“Testosterone receptors, like estrogen receptors, are all over our bodies. We have good data showing how supportive testosterone is for bone health, mental mood, wound healing, depression, cardiovascular health,” said Casperson.

Other doctors who are proponents of more widespread testosterone treatment for women also lament a lack of research on the subject. “My specialty is midlife women’s health and menopause management, and I’m shocked at how little data and recognition there is in female medicine on the role of this hormone,” said Anna Barbieri, an assistant clinical professor of obstetrics and gynecology at Icahn School of Medicine at Mount Sinai.

Barbieri believes testosterone should be looked at as a potentially integral part of hormonal treatment in menopause. But so far, the few trials that have been conducted on the subject have been limited in scope. That was the case with Procter & Gamble’s Intrinsa, a testosterone patch meant to treat HSDD. The maker withdrew its FDA approval application in 2004, after an FDA panel expressed concerns about potential cardiovascular risk and deemed the 24-week study presented to prove the patch’s safety insufficient.

This lack of research leaves a lot of unanswered questions not only about the effectiveness of testosterone in treating various conditions, but about its mechanism of action.

“We actually don’t understand what brings about those effects on a molecular level. Is it the binding to the receptor itself? Is that the action of testosterone in the nucleus? Is there a way for us to predict someone’s response?” said Barbieri. “This has been kind of a forgotten, understudied area of women’s health that really needs exploring.”

Barbieri said she realized how unprepared she was to recognize and treat some of the symptoms of menopause when she was going through it herself — despite the fact that she is a trained OB-GYN. “Many providers really have no training in this area,” she said, which, combined with some reluctance to share sexual problems on the patient’s side, often leads to undertreatment.

One reason contributing to doctors’ limited awareness of the benefits of testosterone for women is the 2002 Women’s Health Initiative (WHI) study. The study, part of ongoing research on women’s health, found that post-menopausal women taking estrogen and progestin had an increased risk of breast cancer, heart disease, stroke, blood clots, and urinary incontinence. Despite also identifying benefits such as better bone density and lower incidence of colorectal cancer, the widely-publicized study led many to consider hormonal treatment dangerous during menopause, and doctors were advised to avoid or limit its use.

Things have changed since then: Further research has shown estrogen treatment is actually linked to reduced breast cancer mortality, and estrogen combined with progestin does not increase its risk. The benefits of estrogen treatment largely outweigh the risk for women who are under 60 years of age and within 10 years of entering menopause. For a majority of women, estrogen is now the recommended first-line treatment for menopause symptoms.

But some doctors who, like Barbieri, were trained or practiced when the WHI’s report came out are still holding onto old notions about hormonal treatment safety. And when they do update their prescription practices, they’re more likely to become aware of the benefits of estrogen than testosterone. “Estrogen in a way is a low-hanging fruit because it’s been studied; we know so much,” said Barbieri.

The hurdles to prescribing testosterone

Agreement on the importance of testosterone treatment is far from universal, even among menopause specialists.

“We lose testosterone slowly over time as we age, but it does not change appreciably at menopause,” said Stephanie Faubion, the medical director for The Menopause Society, a nonprofit focusing on improving treatment and understanding of menopause. “There’s no reason we need to consider it as a menopause treatment.”

Moreover, Faubion said, even though testosterone is used to treat low sexual desire, it is rarely a solution to it. “The majority of low sexual desire in women is not related to a testosterone problem — it’s related to a lot of other things,” she said. While she acknowledges that testosterone treatment may be overlooked by doctors, she said it’s a problem that affects only a minority of menopausal women, in comparison with the larger issue caused by lack of estrogen treatment for menopause.

Even if a doctor wishes to prescribe testosterone, doing so is a whole other hurdle. In 1990, it was added to the controlled substance list of Schedule 3 drugs — a status it shares with low-grade morphine and ketamine — because of concerns that male athletes were abusing it. As with other Schedule 3 substances, doctors need a special license to prescribe it and multiple licenses if they practice in more than one state, such as doctors who provide telehealth services. This is both an added cost and can further dissuade physicians from using testosterone as a treatment option altogether.

Then there’s the fact that there is no actual testosterone product for menopausal women to prescribe. Women have two choices, both of which must be paid for out-of-pocket.

The first option is to use the male gel formulation, which comes in little sachets about the size of a ketchup packet. The dose for women is one-tenth of the dose for men. “You’ve given a woman a packet and you tell her to divide it in 10,” keep it in the bathroom, and make it last for 10 days, Casperson said. “It’s messy. It’s not accurate.” This approach is, however, relatively cheap: A male monthly dose costs about $200 and lasts 10 months for a woman.

A less inconvenient option is getting testosterone at the right dose from a compounding pharmacy. This offers less guarantee of the product’s consistency and quality but at least eliminates the messiness, albeit at a price of $80-$100 per month.

Women who are unable to get prescriptions from their doctors sometimes resort to less safe options: pellets and injections, which can expose them to dangerously high levels of testosterone dosed for men, and side effects that include a painful enlarged clitoris, balding, acne, and deepened voice.

Still, menopause treatments are having a moment, and increased funding for research may result in more attention given to studying testosterone in women. Doctors say they’d welcome an FDA-approved product that’s proven to be effective — so long as companies aren’t “just going to charge $500 and put it in a pink box,” said Casperson. “Male testosterone is very cheap, and if you brand it for women, make the dose one-tenth and jack up the price because now it’s branded, you didn’t help anybody.”