Chapter 138
Vaginal Hormones
But something else should also be taken into account. Based on the SMI test, the World Health Organization recommends an osmolality of no more than 380 mOsm/kg for lubricants and vaginal moisturizers. This is the measure of how concentrated the dissolved ingredients are. And how do you arrive at that value? You smear slugs with cream. SMI stands for slug mucosal irritation, “slug mucosal irritation.” In this test, slugs are coated with lubricants for five days, and the degree to which the slugs’ mucosa is irritated and the tissue is damaged is measured. Below the cutoff, no harmful effect was found for the slugs, but a product like K-Y Jelly with 2463 mOsm/kg led to mild to moderate irritation, and the outliers, such as Astroglide with 5848 mOsm/kg, produced considerable tissue irritation and damage.
Dozens of commonly used lubricants and moisturizers available worldwide were tested, and the only two vaginal moisturizers that met the WHO criteria were the aloe vera moisturizing gel from Ah! Yes VM and the hyaluronic-acid-based moisturizer from Balance Activ. The only lubricants that passed the test came from the brands Yes, Good Clean Love, and System JO, as well as Durex’s Sensilube gel, though their Play Feel lubricant failed.
Vaginal hormones
If over-the-counter lubricants and moisturizers do not sufficiently relieve GSM symptoms, the American College of Obstetricians and Gynecologists and other medical associations recommend low-dose local (vaginal) estrogen, provided the patient has not had a hormone-dependent cancer, such as uterine carcinomas or breast cancer. This is considered safer and more effective than systemic hormone therapy. A meta-analysis of 58 studies comparing vaginal estrogens with oral ones concluded that vaginal estrogen therapy relieved GSM symptoms better. Many women on systemic menopausal hormone therapy additionally need vaginal estrogens to get symptoms under control.
Vaginal estrogens are available as creams, suppositories, and rings. In 30 comparative studies conducted, no differences were found in the effectiveness of the different preparations. However, it can take weeks for noticeable symptom relief to occur, and two to three months before the full effect develops. A one-year study clearly demonstrated the effectiveness of vaginal estrogens, but studies lasting up to twelve weeks were unable to show any benefit over placebos.
Estrogens on the vulva or in the vagina are absorbed systemically and carry the same FDA black box as oral estrogens, which warns in capital letters of an increased risk of “endometrial carcinomas, cardiovascular disease, breast cancer, and possible dementia.” Vaginal estrogen is nevertheless considered safer because it can be used locally in much lower amounts—one hundredth of the oral dose needed to treat hot flashes, for example. The Harvard Nurses’ Health Study found no increased risks associated with vaginal estrogens in an 18-year follow-up. Randomized controlled trials lasting up to a year appear to confirm their safety, but in observational studies, vaginal use was linked with a doubled risk of endometrial carcinomas. One of these studies, however, was conducted in the 1970s, when higher estrogen doses were still being used, and the results of the more recent study from Denmark may have been confounded by concurrent oral estrogen use. To be absolutely safe, women who have survived a hormone-dependent cancer should also avoid low-dose, locally applied estrogen.
Instead, these women could consider locally applied DHEA. Although orally administered DHEA did not seem to provide any benefit, in 2016 the FDA approved DHEA vaginal suppositories for pain due to GSM during intercourse. DHEA is converted locally into estrogen and does not significantly affect systemic hormone levels. The downside is that DHEA has to be applied every evening, whereas estrogen preparations are typically taken twice a week and vaginal rings need to be inserted only every few months. For anyone who prefers pills, there is ospemifene, a tamoxifen-like agent that has a pro-estrogen effect on the vaginal mucosa. However, in the short term it causes even more hot flashes and urinary tract infections, and there are so far only insufficient data on long-term safety.
Soy
Japanese American women have the fewest hot flashes in the United States and also suffer least often from vaginal dryness. Could that be due in part to their higher soy consumption? There are a few studies on topical use of vaginal gels with soy isoflavones that worked significantly better than placebo gels for dryness and pain during intercourse, and in head-to-head comparison about as well as estrogen creams, but it is unlikely that these women apply soy products topically. But you can also just eat soy, right? If older mice are given isoflavones, their blood flow in the vaginal area increases. And in humans?
Most soy dietary supplements failed, but as I show in see.nf/soygsm, the three studies on soy milk and GSM symptoms are promising. A case report from New York suggests, however, that you can overdo it even with that. A 44-year-old woman sought her gynecologist’s advice because of “increased sexual desire that compelled her to bring herself to orgasm about 15 times daily.” A month earlier she had switched to an almost exclusively soy-based diet and was eating a good two kilograms of soy foods daily. She cut back on that now, and three months later her desire had cooled to the point that she “only satisfied herself sexually twice a day.”
Fennel and fenugreek
Fennel seeds, which are actually whole little fruits, have been shown to have a hormonal effect—for example, they significantly relieve menstrual pain, similar to painkillers of the ibuprofen type. Supplements with fennel oil extracts showed no effect against GSM symptoms after menopause, but whole fennel seeds, ground in a controlled double-blind study and pitted in capsules against a placebo, significantly improved menopausal symptoms at a dose of one teaspoon a day.
Topically applied fennel creams are even more impressive. Within eight weeks, 90 percent of the randomized participants who received a vaginal fennel cream and had previously had severe pain during intercourse reported that they now felt no pain at all. Among users of the placebo cream, the pain remained. Dryness, itching, and paleness in the vaginal area also disappeared completely in the fennel group. These extraordinary results were recently successfully replicated. Other studies likewise found significant benefits of vaginal fennel creams with respect to sexual desire, arousability, lubrication, orgasms, and sexual satisfaction.
Fenugreek seeds are also hormonally active, as I document in see.nf/fenugreek. Men randomized to receive fenugreek capsules showed a clear improvement in body composition as well as strength in the upper body (bench press) and lower body (leg press) compared to placebo, along with a significant increase in blood testosterone and twice as many morning erections. The only side effect? Sometimes sweat and urine can smell like maple syrup. (Sounds like added value!)
What about women’s sexual function? The estrogen variant estradiol stimulates lubrication and blood flow in the vagina and facilitates arousal and the ability to orgasm, but sexual desire in men and women is controlled by testosterone. Fenugreek raises both estradiol and testosterone levels, which leads to an increase in sexual desire and sexual function and results in about a doubling of sexual activity compared to placebo. These results relate to women before menopause, but it was later shown that the same dose also alleviates sexual complaints in postmenopausal women. Even so, in head-to-head comparison, fenugreek did not work as well as an estrogen cream.
Male sexual function
“Sex is important for health,” reported the Harvard Health Letter, noting: “Frequent intercourse lowers the risk of heart attack.” In men, however, this seems to be a perfect example of reverse causality. Infrequent sexual activity in men seems to be a sign of cardiovascular disease even independent of erectile dysfunction.