Gender Bias in Medicine: “How Women Continue to Get the Shaft When It Comes to Testosterone Therapies”

Women experience the loss of sex drive at the same rate as men and have more prevalent symptoms due to the loss of the reproductive hormones estradiol and testosterone.^1–4 Yet, although testosterone replacement therapies and medications for men remain a billion-dollar industry, there is a paucity of options for women.

This would make one think there are not any good solutions for women. But this belief could not be further from the truth. There are in fact a number of evidence-based medical solutions.^5–8 Unfortunately, however, there is also a significant gender bias in the treatment of menopausal women, and the Food and Drug Administration (FDA), the medical community, and supporting medical organizations have turned a dismissive patronizing blind eye to these women.

Nothing exemplifies this point so perfectly as the need for testosterone therapies in women. Testosterone deficiencies in women, especially prevalent in the years before and during menopause, can cause a wide variety of symptoms—including mood disorders, weight gain, cognitive impairment, insulin resistance/diabetes, and low libido, among many others.^4,9,10

Despite these potentially life-changing symptoms, there are zero FDA-approved testosterone products for women. Instead, many women turn to hormonal specialists who can prescribe compounded testosterone.

These compounded hormone products, however, are often a regular target of some in medicine who cite research while attacking them. ¹¹ This research is often affiliated with medical organizations, societies, and pharmaceutical companies that seem to have an interest in preserving the status quo of limited and clinically obsolete FDA-approved treatment options for women. In addition, much of the research to date has focused on men with information extrapolated to women, even though this is physiologically and medically inappropriate.

It is highly problematic when “experts” of clinical guidelines or the organizations that publish them have substantial commercial conflicts of interest (see, e.g., Table 1).^11–13 In addition, when scientific evidence is suppressed or valid arguments or deemed controversies are completely ignored, it contaminates the intellectual integrity of the process and recommendations. Nowhere in medicine is this contamination so clear as the guidelines that address women's hormonal needs for both estradiol and testosterone.

Table 1.

Checks Indicate Known Flaws in the Global Consensus Position Statement on the Use of Testosterone Therapy for Women

√	Sponsor(s) is a professional society that receives substantial industry funding
	Sponsor is a proprietary company, or is undeclared or hidden (Unknown)
√	Committee chair(s) have any financial conflict
√	Multiple panel members have any financial conflict
√	Any suggestion of committee stacking that would preordain a recommendation regarding a controversial topic
√	Failure to acknowledge legitimate controversy
	No or limited involvement of an expert in methodology in the evaluation of evidence
√	Unanimous agreement of panel members (artificial unanimity of recommendation)
√	No external review
√	No disclaimer
√	No inclusion of nonphysician experts/patient representatives/community stakeholders

For Davis et al. ¹⁴ Institute of Medicine red flags that cause concern about trustworthiness of guidelines/consensus statements. ¹⁶

The “Global Consensus Position Statement on the Use of Testosterone Therapy for Women” was used by the newly released National Academies of Sciences, Engineering, and Medicine report as well as recent journal articles to draw the conclusion that there is no medical need for testosterone use in women.^14,15 However, when one reads the list of the authors, ¹⁴ it is a “who's who” of big pharma players. The listed authors only address their own recent pharmaceutical-sponsored randomized clinical trials as being valid; they totally ignore any other data, implying the data itself do not exist. ¹⁴

The “consensus” was formatted to appear as “guidelines,” but there was no peer review process. The article itself is both biased and flawed, as are the Endocrine Society's guidelines on androgen therapy in women. They have no evidence to recommend against compounded hormones, and in fact proclaim that many of their recommendations are based on “expert opinion,” which in itself is problematic. These so-called experts do not routinely treat women using testosterone, so how can they make properly informed recommendations?

Compare this consensus statement with the 2019 publication “Testosterone Insufficiency and Treatment in Women: International Expert Consensus,” which was released by a group of established experts in the field of compounded bioidentical hormone replacement therapy. This group of experts had >100,000 patient-years' experience with testosterone supplementation in women. ¹⁰

This real-world experience coupled with the roughly 100 references/studies (vs. the 1 meta-analysis/14 references in the mentioned Davis et al., testosterone consensus) guided their recommendations, which included:

Testosterone is not a male-exclusive hormone. It is the most abundant gonadal hormone throughout a women's life.

Serum testosterone levels do not correlate with symptoms of testosterone deficiency in women. Optimal ranges of serum testosterone levels in women have not been established.

Female testosterone insufficiency is a clinical syndrome that may occur during any decade of adult life.

Testosterone therapy may be breast protective.

Testosterone insufficiency in women negatively affects sexuality, general health, and quality of life. Supplementation may positively influence sexuality, general health, and quality of life.

Testosterone insufficiency may be associated with an increased risk of cardiovascular disease in women.

Testosterone optimization may be brain protective and may enhance cognitive function.

Testosterone optimization may be a key component for improved bone health.

Testosterone therapy in women has no adverse effects on lipids and/or cardiovascular risk.

Studies of testosterone supplementation show benefits exceed the risk and that consistent purity and potency can be achieved.

This report by true expert frontline physicians with substantial experience and minimal conflict of interest should be given considerable weight by organizations crafting guidelines or authors of articles addressing female hormone replacement. At the very least, the publications should recognize the counterarguments to provide substantive balance to their articles.

The sad truth is that the failure to approve a female testosterone product began over two decades ago. This failure is not only alarming, but also embarrassing to the medical profession as a whole due to our inability to provide equal access to essential hormones that have been made available for men, but not to women.

The medical community and pharmaceutical industry need to do better at addressing this outage, but until then, the compounding pharmacies and compounding outsourcing facilities are filling the void of this unmet clinical need. As patient advocates, it is important to remember the unique needs of our patients—in particular, women—and we must fight to protect our abilities to treat them as such. The time has come to eliminate the gender bias that has plagued our profession. Our female patients deserve much better.