Nearly two million women in the U.S. will enter menopause this year. So, what does the research tell us about the best methods to alleviate menopausal symptoms? Here’s our first story.
Testosterone is linked with sexual desire in both men and women. Women normally produce testosterone throughout the life cycle. Although postmenopausal ovaries continue to produce testosterone, levels naturally decline with age. Testosterone blood levels decrease approximately 50 percent by age 50, which may play a role in the decline in libido (using masturbation frequency as a partner-independent proxy). A syndrome of “female androgen deficiency” symptoms has been popularized, but there is no evidence testosterone “replacement” helps with mood or well-being, hot flashes, or bone, cardiovascular, or metabolic health. The only evidence-based reason to try testosterone in postmenopausal women is for the treatment of low sexual desire that’s causes distress.
A systematic review and meta-analysis of three dozen randomized controlled trials involving more than 8,000 women found that testosterone treatment significantly increased postmenopausal sexual desire. The increase in frequency of “satisfactory sexual events” was statistically significant, but not clinically significant enough to warrant FDA approval, especially given the uncertainty about long-term side effects. The women on testosterone only logged a little under one additional satisfactory sexual event a month, compared to placebo.
Currently, there are more than thirty FDA-approved testosterone products for men, but none for women. Clinicians can trial a few months of a male transdermal testosterone preparation at one-tenth the dose or less, making sure to check levels to prevent overdosing, which can have virilizing side effects, such as clitoral enlargement and voice changes. Even at premenopausal physiological doses, testosterone can cause acne and excessive hair growth on the chin, cheeks, and upper lip. Unlike oral testosterone, formulations administered through the skin don’t appear to have the same negative effects on cholesterol levels, but long-term safety data for women regarding cardiovascular, cancer, and cognitive outcomes are lacking.
It has been estimated that more than a fifth of prescriptions for male testosterone products are actually written for women, and this is not including custom-compounded testosterone. A consensus position statement of international medical societies specializing in hormone issues recommends against compounded “bioidentical” testosterone due to the lack of evidence for efficacy and safety. Similarly, the dietary supplement DHEA, which can convert into testosterone within the body, cannot be recommended for low libido in women, since a meta-analysis of more than 20 randomized controlled trials found no significant effect on improving desire and sexual function.
Are there any natural ways for women to raise their testosterone levels? Listening to music for just 30 minutes can increase testosterone levels in young women by about 20 percent. Interestingly, the opposite effect is found in men. For more on the effects of music, check out my video Music as Medicine.
Heavy mint consumption may lower testosterone levels in both men and women. There are case reports of men drinking four cups (0.95 L) of day of spearmint or peppermint tea losing their sex drive. Given the apparent anti-androgenic effects, researchers decided to try it out on women concerned about excessive hairiness, and in a matter of just five days, were able to drop their free testosterone levels by about 30 percent with two cups (0.50 L) of mint tea a day. There’s a syndrome called PCOS, or polycystic ovarian syndrome, which can result in abnormally high testosterone levels in women, which can be successfully brought down with mint tea. But for women struggling with low libido, it might not be a good choice.
In my next story – we look at the different health risks of vaginal and oral estrogen.
The first-line treatment for mild to moderate vaginal dryness due to menopause are lubricants and moisturizers, and I called out the safest brands. If over-the-counter lubricants and moisturizers are insufficient to control the genitourinary symptoms of menopause, low-dose, local estrogen therapy is recommended, unless women have a history of hormone-dependent cancers like endometrial or breast.
Local, meaning applied vaginally, as opposed to taken orally. Vaginal application is considered safer and more effective than systemic hormone therapy. A meta-analysis of 58 studies comparing vaginal to systemic estrogens found that vaginal estrogen therapy offered better symptom relief than estrogen pills, patches, or implants. In fact, many women who are on systemic menopausal hormone therapy have to add on supplemental vaginal estrogens to control symptoms.
Vaginal estrogens are available as a variety of creams, suppositories, and rings. Thirty randomized, control comparative trials have been performed, and there appears to be no difference in efficacy between the various preparations. However, they may take weeks before a noticeable alleviation of symptoms is detected, and two to three months before the full effect is achieved. Although year-long studies can clearly demonstrate vaginal estrogen’s benefit, studies as long as 12 weeks have failed to manifest superiority to placebo.
Some of the estrogen applied to the vulva or vagina is systemically absorbed, and therefore conveys the same black box FDA notice that oral estrogens carry, an all-caps warning of increased risk of “endometrial cancer, cardiovascular disorders, breast cancer and probable dementia.” Vaginal estrogen is considered safer, though, since it can be used at a much lower dose (as low as one-hundredth the oral dose). The Harvard Nurse’s Health Study did not find any increased risks associated with vaginal estrogen use over 18 years of follow-up. Randomized controlled trials lasting up to a year appear to confirm its safety, but there have been observational studies linking vaginal use to about a doubling of odds for endometrial cancer. But this was done back in the 1970s when higher estrogen doses were used. And a more recent study out of Denmark that found the same thing may have been confounded by concurrent oral estrogen exposure. Out of an abundance of caution, though, even low-dose localized estrogen may be contraindicated in hormone-dependent cancer survivors, to be on the safe side.
Breast cancer survivors suffering from GSM may want to consider vaginal DHEA instead. Oral DHEA doesn’t appear to offer any benefit, but in 2016 the FDA approved vaginal DHEA suppositories for pain during intercourse due to menopause. It’s converted locally into estrogen, and does not significantly affect systemic hormone levels. A downside is that it has to be administered nightly, whereas estrogen preparations are typically twice a week, or even every few months with the vaginal rings. For those who would rather an oral treatment, there’s ospemifene, a tamoxifen-type drug that has pro-estrogenic effects on the vaginal lining. However, it can actually double the rate of hot flashes and urinary tract infections in the short-term, and insufficient data is available for long-term safety.
Finally today, we look at what behaviors or circumstances cause variability in the onset of menopause.
Since 1970, the proportion of women having their first child after age 35 increased nearly tenfold. This may introduce a ‘‘longevity penalty’’ on their children (as those born to older mothers don’t tend to live as long), but mothers having children later tend to live longer themselves. For example, female centenarians were found to be nearly four times more likely to have had children after age 40 than women who died by their 70s.
This doesn’t necessarily mean delaying kids will make you live longer. Smoking, for example, could be a confounder—causing both early menopause and an early death. Or maybe delayed reproductive aging is just a sign of slower aging in general. However, some have suggested the biological changes of pregnancy might have a rejuvenating effect, even going so far as to suggest a parabiosis mechanism—bathing in the blood of babies, but just not in a Countess Báthory sort of way. To sort between these possibilities, researchers studied the longevity of brothers of women who gave birth after age 45, and that of their wives. The brothers with late-fertile sisters lived longer, but their wives did not. This suggests a genetic robustness cause, rather than a rejuvenation effect, and the fact that the longevity benefit didn’t extend to their wives suggests it’s not due to a confounder like socioeconomic strata.
On the other hand, women who experience extremely early menopause (the one percent who stop menstruating by age 39) may be at risk for diminished longevity, and should, therefore, be counseled to adopt a particularly healthy diet and lifestyle. Approximately half of the variability of age of menopause between women is explained by genetics. Other than smoking, what other behaviors or circumstances can help explain the rest?
Factors that don’t appear to affect the age of menopause include exercise, obesity, alcohol, coffee, or vitamin D status. Interestingly, women who’ve been married tend to arrive at menopause later. Some suggested it may be the influence of male pheromones (given the fact that exposure to male armpit odor makes women’s cycles more regular). But it turns out that male cohabitation alone doesn’t appear to matter. It may be the sex. Married older individuals tend to have more sex, and indeed, pre- and peri-menopausal women, average age 46, who reported sex weekly were 28 percent less likely to experience menopause over the subsequent decade than those reporting sex less than once a month. You can very well imagine how this could be a result of reverse causation, though. Instead of more sex leading to later menopause, a later menopause may have instead led to more sexual engagement.
The relationship between tobacco use and early menopause is thought to be mediated by the toxic effects on the ovaries of the polycyclic aromatic hydrocarbons (PAH) in the smoke. Among nonsmokers, this PAH exposure is almost entirely from food––mostly grilled, barbequed, and smoked meats. Could this explain why, in the Harvard Nurses’ Health Study II, higher plant protein intake was associated with a significantly lower risk of early menopause? Feed female monkeys a diet high in animal protein, and not only did they get more atherosclerosis, but also an acceleration of ovarian aging. Now, in the original Harvard Nurses’ Health Study, animal protein consumption was associated with infertility, such that replacing even replacing five percent of animal protein intake with plant protein could potentially cut the risk of infertility in half. But in the Nurses’ Health Study II, while plant protein appeared to delay menopause, animal protein intake was not associated with menopause age either way. And in the UK Women’s Cohort Study, those eating more animal protein were six percent more likely to experience a later menopause. The data is similarly conflicting in vegetarians.
Some studies found no difference, or a later age, of menopause in vegetarians. But others found an earlier age compared to nonvegetarians. For example, the largest study found that vegetarians reached menopause at an average age of 50.1 years, compared to nonvegetarians at 50.7 years. As I noted, premature menopause before age 40 may be detrimental for longevity, but being a little earlier within the normal range may actually be beneficial for cancer risk.
At the same age, breast cancer risk is about 40 percent higher in premenopausal compared to postmenopausal women––presumably due to higher exposure to the “necessary evil” hormone estrogen. Breast cancer risk is three percent higher for every year later a woman starts menopause, and five percent higher for every year earlier a girl starts menstruating. (On average, women whose periods hold off until age 15 appear to live the longest.) Vegetarian women tend to have lower estrogen levels, perhaps due to higher fiber intake, and interventional studies show that switching to a more plant-based diet can reduce circulating estrogen levels by more than 40 percent.
This could help explain why vegetarian girls may hit puberty later, and why those eating strictly vegetarian not only have lower cancer risk overall, but particularly lower risk for female-specific cancers. Age of menopause may not be a factor though, based on an interventional trial randomizing women on the verge of menopause (average age 49) to two years of a lower-fat diet to reduce breast cancer risk. The intervention group ended up eating more fiber (and, therefore, more plant-based), but though they did experience improvements in mammogram findings, the dietary shift failed to influence the timing of menopause.
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