“What about testosterone replacement as a treatment for Menopause and Perimenopause? My friend told me the testosterone pellet has changed her life!”- If you’re a female in your menopause/perimenopause era you’ve either been the one to sing the praises of the pellet, or you’re the cautiously optimistic friend that wants more information. Either way, you’ve come to the right place!

Let’s start with the basics:

Testosterone is a natural steroid that is “anabolic”- meaning it builds muscle, and “androgenic” meaning it promotes male sex characteristics. It is produced by the testicles in males and by the ovaries in females. Additionally, your adrenal gland produces a hormone called DHEA- which is also converted to testosterone and estrogen in differing amounts in males and females.

Testosterone is the main medication used in gender affirming care for a patient that was assigned female at birth, to promote the development of secondary sexual characteristics typically associated with those assigned male at birth. It is also used to treat states of low testosterone in males- which we will talk about another day.

So why am I bringing it up in a series of posts about menopause?

Testosterone is currently being utilized as a treatment to boost energy, mood, cognition, enhance general well-being, reduce body weight and improve libido in perimenopausal and menopausal females.

Just another example of how the Women’s Health Initiative study completely derailed the management of menopause by primary care doctors (family medicine, internal medicine, even gynecologists were impacted!).

To be clear, it is not the study itself I blame. The results of the Women’s Health Initiative and subsequent changes in the medical management of hormone replacement therapy have saved countless lives. The results of the study also formed the basis of follow up studies (ELITE and KEEPS) that helped to identify ideal candidates for HRT while providing physicians with a comprehensive risk/benefit profile to help patients with informed decision making. The follow-up studies also gave us evidence-based indications for HRT and helped determine optimal timing for both treatment initiation and weaning/cessation to minimize associated risks and maximize potential benefits.

However, it has also resulted in complacency and hesitation in the training and management of women’s health, more specifically, the hormonal management of menopausal symptoms. The results of the WHI study shocked the medical community, and many have not updated their practice to include the results of newer, more accurate studies.

It’s over 20 years later and women’s health still hasn’t recovered.

My residency training on hormone replacement therapy in menopausal females included the following:

“We don’t do that, it’s too risky. It causes breast cancer, endometrial cancer, and increases the risk of stroke and heart attack. Refer to gynecology.”

For those of us with an interest in women’s health we were given education (and did our own research) on non-hormonal options for the management of menopause- because many of these treatments were already familiar for different indications, they were seamlessly implemented into our practice, and menopause was just another use for these medications.

There is absolutely a role for the non-hormonal management of menopausal symptoms, and I am grateful to be able to provide women with several treatment options.

Hormone replacement therapy remains an effective, and safe treatment in the management of the vasomotor symptoms of menopause. This is something that those with an interest in women’s health have had to teach themselves through continuing medical education, post graduate training and researching medical literature.

For those with no interest in women’s health, they were taught to refer to gynecology and are still comfortable doing just that.

To be perfectly clear, this situation was not unique to my residency program; it was the standard and remains fairly common practice. With studies as recent as 2018 revealing that primary care and gynecology residents reported a low level of comfort with managing menopausal symptoms. Fortunately, more recent data suggest a gradual improvement in physicians’ level of comfort with the hormonal management of menopause.

But, what about the comfort level of our patients?

Back to the testosterone debacle- women have reported (and still do) that they do not feel their doctors take their menopausal symptoms seriously and feel that they do not understand the impact that these symptoms have on their quality of life. That coupled with the hesitance to prescribe HRT has led women to seek treatment for menopausal symptoms with non-traditional options, outside of primary care and gynecology. Amongst these non-traditional offerings are, you guessed it, testosterone pellets.

Now that you have this background, we are ready to talk about the science and data behind testosterone pellets.

When it comes to the use of testosterone in females, the indications are limited (*at this time), but moreover, they pose significant risk of side effects. The only indication (*at this time) for testosterone replacement in females in the United States is the treatment of low libido. This is not FDA approved and would constitute off label usage.

*It is certainly worth looking into the role of testosterone replacement in female patients for indications beyond low libido, but I would not make a blanket statement about its benefits before we have concrete data. We already did that with estrogen/progesterone and we’ve since learned, that while these are great options for some, they may not be the right option for all– and it is important to consider the risk/benefit profile at an individual level.

So here is the truth- androgens- like testosterone, DHEA and DHEAS, play a role in female sexual function, the magnitude of this role is uncertain.

To better understand the science- let’s first go over the normal physiologic ranges for male and female testosterone levels:

These numbers are from the Mayo Clinic- I think it’s fair to say that male testosterone levels are generally 10x higher than physiologic female levels.

Age	Male normal testosterone range	Female normal testosterone range
11 to 15	Less than 830ng/dL	Less than 79 ng/dL
16 to 17	102 to1010ng/dL	Less than 79 ng/dL
18-99	193 to 824ng/dL	Less than 40 ng/dL

There are no long-term studies to support the safe use of testosterone supplementation in females to boost energy, mood, cognition, enhance general well-being and reduce body weight.

While studies have not consistently demonstrated a correlation in androgen levels and female sexual function, supraphysiologic doses (nearly 10x the maximum physiologic level for females) of androgen therapy have been shown to increase libido and sexual frequency. That means the lower range of normal for a male is where a female may show improvement in libido.

Though off label, female hypoactive sexual desire may be treated with topical forms of testosterone at the lowest effective dose, for the shortest duration. Unfortunately, the data is conflicting and bringing the testosterone levels to the high normal range for females, does not necessarily produce any benefit in libido.

So, why can’t we just increase testosterone to the low-normal levels seen in males? What’s the harm? Great question, more on that below.

Here are the consequences of excess testosterone in females:

• Acne
• Excess facial/body hair
• Deepening of the voice
• Receding hairline
• Menstrual irregularity
• Mood instability (rage)
• Clitoral enlargement

There are no studies to support the long-term use of testosterone in women. Concerns with the long-term use of testosterone in females (greater than two years) include the following:

1. Increased risk of breast cancer
2. Negative impact on your lipid profile (increase LDL, decrease HDL)
3. Can cause liver damage (specifically with oral supplementation)
4. Increased risk of stroke
5. Increased risk of heart disease

Again, much like the findings of the WHI study and hormone replacement therapy.

Furthermore, testosterone pellets exert their effects for 3 months, meaning that if you are dosed incorrectly, you will have to deal with the side effects of that dosing for ¼ of a year. Both testosterone injections and pellets have the potential for very high testosterone levels.

If you do decide to trial testosterone therapy for low libido, topical formulations at 1/10^th of male dosing are the ideal starting point. Benefits, if they are to be seen, would be evident in 12 weeks, with a plan for discontinuation in 6 months if no significant improvement is noted.

Here is a clear summary of the practice guidelines for the use of systemic testosterone in the treatment of hypoactive sexual desire disorder in women- from the International Society for the Study of Women’s Sexual Health

Final thoughts on testosterone pellets and implants:

1. Though testosterone may seem like a tempting option, it really feels like a Deja-vu waiting to happen, especially when you consider the fact that a significant portion of testosterone in females, is converted to estrogen.
2.  It is expensive and unregulated, with a high potential for supratherapeutic dosing where side effects can be highly unsettling. No long-term studies to support its use, and none to support the indications for which it is currently being marketed (to boost energy, mood, cognition, enhance general well-being and reduce body weight) Though it may seem safer than estrogen, there is nothing to suggest that this is medically true. In fact, it may be worse, given that we know how to monitor estrogen, and when/ in whom it can safely be started
3. The medical community has a long way to go in winning back the trust of our menopausal and post-menopausal patients.

I hope this information has been helpful and provides some clarity around an otherwise confusing topic. Hopefully someone will do more research on the use of testosterone in females, I’ll be sure to update as new data surfaces!

Sincerely,
Corsano MD- Your friendly neighborhood PCP

womens health and testosterone.pdf
Testosterone Levels In Women – Mayo Clinic Press
Testosterone: What It Is, Function & Levels
Testosterone therapy for women: Can it improve your sex life? – Harvard Health