I was asked by many friends why there is no FDA approved testosterone preparation for women in 2020 after my recent presentation on my new YouTube channel “Integrative Endocrinology with Beatriz Olson”, on the value of testosterone replacement for women who are bothered with low libido and have hypo-sexual dysfunction disorder (HSDD)?
This is an amazing story of a patriarchal medical system that gives access of testosterone and Viagra to men, but cannot approve small amounts of testosterone for women; cultural norms and delays in acknowledging that women’s sexual issues matter; and the financial forces involved to create and give access of useful products for women. In addition some argue that we are medicalizing normal events, like menopause or women’s sexual dysfunction as we age, to sell pharmaceutical products.
The story is further complicated by the fact that women’s sexuality is extremely complex and quite different that of men. Women’s sexual desire and function involves multiple parameters including sense of physical health, psychological safety, trust, privacy, and emotional sense of relationship wellness. All this comes first, then we have the effect of hormones on the mind and genitalia.
Testosterone levels drop in women as we age and more rapidly for women who have surgical removal of their ovaries. In women testosterone levels do not correlate with who has deficiencies and who does not. What we do know is that if testosterone levels are increased, from whatever the baseline is, there is improvement in multiple domaines of sexual function in women.
Nonetheless, the fact remains for women their brains are their greatest sexual organ, such that intimacy with a new desired partner rekindles sexual function and overrides any hormone deficiency.
However for women in long-term relationships who are not considering new partners, and experience decrease in desire, arousal, and pleasure, testosterone may help.
The story of why the latest testosterone patch, Intrinsa, for women was not approved by the FDA follows, as well as why I decided to do my own research so that I could treat women with testosterone more safely.
After many years of research led by various investigators showed that testosterone helps women’s sexuality, finally the most promising testosterone patch, Intrisa, for women was available and tested in a placebo controlled method in women with and without hormone replacement therapy (HRT), and it helped every group. I must give a shout out to Dr. Susan Davis, an Australian (Melbourne) investigator who was the leader in many of these published studies, she has been an academic champion for women’s sexual health for decades, and a role model for me. The findings of these studies showed that a testosterone patch that delivered 300 µg of testosterone through the skin daily could increase arousal, sexual desire, and pleasurable sexual events in women. The effects could be seen at 12 weeks and maximum affect was achieved after 24 weeks of treatment. Levels of testosterone remained stable over time, slightly above the normal range, free testosterone of about 6 pg/mL. Many women went on to continue the study for a whole year. There was a significant improvement in the satisfaction of women that were receiving the patch, so much so that even though there was a mild increase in hair growth in some women, women were willing to deal with this nuisance, by waxing or other methods, to continue to take this patch to maintain their improved sexual function.
The FDA did not approve Intrinsa because it only increased the number of satisfactory sexual events to 2.1 extra sexual pleasurable events per month when compared to women getting placebo patch (0.7 additional sexual pleasurable events per month). The final reason for the lack of approval was lack of long term safety data. What was not discussed was that prior to the use of testosterone, most women were having sexual encounters with their partners, dutifully, even though they were not enjoying the experience, and that after the use of the testosterone patch their sexual interactions with the partners became significantly more pleasurable. I think you and I would agree that this matters!. There was also a significant increase in desire and decrease in distress. The FDA was looking for a significant increase in sexual events per month rather than focusing on the significant finding of how meaningful it was for women to have their sexual encounters actually be enjoyable. The patch also had no worsening effect on cholesterol levels and thus did not suggest that it would increase risk of heart disease. Additional it did not change or increase levels of other sex-related hormones (estrogen, DHEA, or sex hormone binding globulins) suggesting that that it would not increase risk of breast cancer. Now in 2020 it is increasingly clear that testosterone actually decreases breast cancer risk.
The Intrinsa Patch also underwent FDA evaluation just 2 years after the Women’s Health Initiative (WHI) study had been published in 2002. This study put a stop to the practice of hormone replacement therapy for the following generation of women who needed it. The WHI study tried to study if giving the non-bioidentical hormones conjugated estrogen (Premarin) and progestin (Provera) to older women, at risk of heart diseases, would decrease heart attacks or strokes. These women had not received postmenopausal hormones for years. This study found that if you give older women oral, non-bioidentical, estrogen and progestin, after many years of not having hormones, some bad things happen. These included increased risk of stroke and heart attack in groups taking oral Premarin (which increases clotting factors by the liver with or without progestin), and increased rate of breast cancer in the Premarin with progestin group (progestin, a non-bioidentical progesterone that increases breast cancer risk). Incidentally breast cancer risk was actually decreased by 24% in women who did not have uterus and used estrogen alone, even though it was Premarin. We now know we shouldn’t give estrogen and progesterone to women that have not received hormones for 10 years or more after the menopause. Then, though, the fear of approving another hormone like testosterone after the progestin fiasco was not palatable: In the minds of the FDA evaluation panel, these risks could not be taken on to achieve a measly two extra sexually pleasurable events per month. The Intrinsa patch was not approve in the US.
In Europe the Intrinsa patch was approved with the limited indication for low libido after surgical menopause. Subsequently Proctor and Gamble, manufacturer of the patch, asked for approval to be used in menopausal women that did not have surgical menopause but had low libido. In all studies of these women it has been shown that adding the Intrinsa patch of 300 µg per day could improve sexual pleasure and all parameters of the sexual domain. However no approval was given and the limited indication for use of the testosterone patch made the maintenance of the patch and its brand not worth the expense of making the drug.
That was the end of any FDA approved testosterone product for women ten years ago. Since then, women who have low libido either use men’s preparations or get testosterone in compounded preparations that are not generally regulated for quality and not approve by conventional medicine medical societies. There is no published data in women using these latter options. Recently there has been approval of a new non-hormone drug called flibanserin (Addy). It has a different mechanism of action in the brain, and from my experience prescribing it to patients has led to significant un-desirable psychiatric side effects.
My testosterone research study was published in the Journal of The Endocrine Society this year. I used very low doses of testosterone 0.5-2 mg per day 6 days a week in post menopausal women with low libido. Levels were tested after 12 weeks of administration. The purpose was to see if I could achieve safe levels of testosterone with doses frequently used by compounding pharmacies. In my study the testosterone was compounded by only one pharmacy, so I did not have to deal with the possible inter-pharmacy variations. I have no financial involvement with this pharmacy, which was unaware of the research. After testing analysis of 4 modes of preparations: cream to the skin, cream to the vagina, vaginal suppository, or vaginal oil capsule, my research shows that 2 out of the 4 methods of administration of these tiny doses is pleasant and effective. One of the better methods is as a cream to the skin and the other is as a vaginal capsule in oil. Many of my patients were on HRT, some of my patients who could not use HRT or were older. These low doses and preparations significantly increased testosterone levels in women to upper normal pre-menopausal testosterone levels. These low doses of testosterone also have little to no side effects to patients during the time of observation over the past 2 years. Rare side effects reported were 1 episode of acne and 1 with some hair growth. Both patients chose to stay on the testosterone but at lower doses. The lowest dose that achieves the goal for each patient is best. I also noted that I could decrease the doses with time while maintaining good levels. The longest published studies on testosterone use in women have lasted 2 years.
My thoughts beyond my data are that low doses and gradual adjustments are the way to achieve health goals for now. While this research on nearly 50 women helps the journey of treatment for women, from looking at years of published research, it is my opinion that testosterone is additionally helpful in improving bone mass and muscle mass in women. This may be particularly useful in older women who have osteoporosis and frailty, both of which increase risk of fractures, but also for early postmenopausal women who have osteopenia and low sex drive. It is also a helpful addition to HRT in women that are expecting to stay on HRT for the long run to maximally decrease mild but potential negative effect of long term estrogen exposure on breast tissue.
I hope we can soon have a consistent FDA approved preparation that is widely available for women with a safety margin and efficacy that I can trust.
Note bene:
Normal testosterone levels do not cause breast cancer, do not cause heart disease, and do not make you manly or aggressive . Testosterone increases libido, increase motivation, increases muscle mass and strength, and prevents breast cancer.
Very high doses of testosterone, in the normal range for men, can cause male-pattern hair loss, hair growth in unwanted places, deepening of the voice which is not reversible, clitoral enlargement and mood changes. When I restored testosterone to the normal upper range for women, I did not see these problems. Testosterone should not be given by injection due to increased risks of heart disease. Testosterone should not ever be taken orally due to increased risk of liver damage. Additional testing with a Dutch urine test can be done to determine if you metabolize testosterone in a manner which could potentially harm you. This Dutch test can also be used to find out how you can metabolize your HRT better.
References:
1. Olson, Beatriz. Compounded testosterone preparations raise testosterone levels to premenopausal ranges in postmenopausal women with hypo-sexual desire disorder (HSDD). Journal of The Endocrine Society, Vol 4, Supple 1, April-May 2020.
2. Davis S et al. Testosterone for low libido in postmenopausal women not taking estrogen. New Eng J Med 2008;359:2005-17.
3. Davis S, Parish S. Testosterone in Women: Can the challenges be met? The Lancet Diabetes and Endocrinology. Vol 3:588-589, Aug 2015.
4. Spark RF. Intrinsa fails to impress the FDA advisory panel. International J of Impotence research 17, 283-4, 2005
5. Islam RM etal. Lancet Diabetes Endocrine 2019, July 25, 2.
6. Davis SR. Climacteric, 22:5,429-434, May, 2019.
7. Davis SR JAMA 2005;294:91-96.
8. Elraiyah T et.al. J Clinical Endocrinol, 2014;99:3536-42.
Be well and check out my new youtube:< Integrative Endocrinology with Dr. Beatriz Olson> its perfectly imperfect but I am trying to authentically help you.