The Truths of Testosterone Restoration Therapy in Females

by Jim Paoletti, BS Pharmacy, FAARM, FIACP – Director of Education | Power2Practice  

There appears to be many assumptions, questions and concerns surrounding the use of testosterone therapy in women. It has been written that testosterone is a male hormone, that its only benefit to women is to increase sex drive, and that testosterone therapy will result in masculinization of a female. It has also been stated that testosterone in females causes hoarseness and voice changes, hair loss, liver damage, and aggression. And that testosterone replacement has adverse effects on the heart, may increase the risk of breast cancer, and that the safety of testosterone use in women has not been established.

Many factors lead to these false conclusions. Often, something repeated often enough is eventually believed, even when adequate evidence is lacking. Epidemiological studies implicating elevated endogenous testosterone levels with certain disease states are misleading because there is not enough evidence to support a causative role. Confusion concerning the safety of testosterone therapy is often the result of extrapolation of adverse events from high doses of anabolic steroids despite a lack of evidence for such.

If the myths and misconceptions concerning Testosterone use in women are replaced with the science of physiology, biochemistry and evidence, the benefits of testosterone in the female become obvious.

Testosterone’s Role in Female Health

Testosterone is not a “male only” hormone. It’s the most abundant biologically-active female hormone. Testosterone’s role in women’s health goes well beyond sex drive and libido. Androgen receptors are located in almost all tissues, including the breast, heart, blood vessels, GI tract, lung, brain, spinal cord, peripheral nerves, uterus, bladder, ovaries, vaginal tissue, endocrine glands, skin, bone, bone marrow, synovium, muscle and adipose tissue. As early as 1937, testosterone was used to successfully treat the symptoms of menopause. Testosterone has been used to treat signs of androgen deficiency in females, including mood swings, anxiety, depression, irritability, tearfulness, fatigue, bone loss, muscle loss, memory lapse, and hot flashes, as well as sexual dysfunction.

While supra-physiologic doses of synthetic androgens or testosterone can cause increased facial hair growth, hirsutism, and slight enlargement of the clitoris, a physiologic dose of bioidentical testosterone does not have a masculinizing effect on females or female fetuses. While a few small anecdotal case reports and questionnaire studies reported an association self-reported voice changes and 400 to 800 mg daily of the synthetic androgen Danazol, prospective, objective studies demonstrated the opposite. There is no conclusive evidence that testosterone therapy causes hoarseness or irreversible vocal cord changes in women at physiologic doses. Hoarseness is common, affecting 6.6% of the adult population, and more prevalent in women than men. Common causes of hoarseness are inflammatory related changes. Testosterone deficiency is listed as a cause of hoarseness, which is consistent with the anti-inflammatory properties of testosterone.

What About Hair Loss?

Contrary to the popular notion, testosterone therapy can increase scalp hair growth in females. There is no real evidence that testosterone therapy is a cause of hair loss in men or women. Hair loss is a complicated, multifactorial genetically determined process that is not completely understood. A metabolite of testosterone, dihydrotestosterone (DHT) is thought to be the active androgen in male pattern baldness and female “androgenic” alopecia. Although women with PCOS have elevated testosterone levels and hair loss, this does not prove causation. PCOS patients also have insulin resistance, and hair loss is common in both men and women with insulin resistance. Both obesity and insulin resistance increase 5-alpha-reductase, the enzyme which converts testosterone to DHT. Hair loss can also be caused by low testosterone and/or elevated estrogen as seen with increased aromatase activity in obese patients. One report showed that two thirds of 285 female patients treated with testosterone showed increased hair growth. Women who did not re-grow hair were more likely to be hypo or hyperthyroid, iron deficient, or have elevated body mass index.


Testosterone & Cardiovascular Disease

There is substantial evidence that testosterone is cardiac protective and that physiologic levels decrease the risk of cardiovascular disease. In fact, there is overwhelming biological and clinical evidence that testosterone is cardiac protective. Testosterone had a beneficial effect on lean body mass, glucose metabolism and lipid profiles in men and women. It has been used to successfully treat and prevent cardiovascular disease and diabetes. Testosterone acts as a vasodilator, has immune-modulating properties that inhibit atheromata, and has a beneficial effect on cardiac muscle. It has been shown to improve functional capacity, insulin resistance, and muscle strength in women with congestive heart failure.


Delivery Methods

I have heard it stated often that testosterone should never be given orally in men or women. This claim is based on the assumptions of (1) poor absorption (2) potential liver toxicity and (3) excessive conversion to estradiol. “Poor absorption” is a relative term. One pharmaceutics textbook from my college days stated not to give testosterone orally because only 1 mg out of 6 mg was absorbed. But that was before hormones were micronized, which increased absorption substantially. Also, the result was 16% absorption, which is greater than some of the pharmaceutical drugs prescribed.

Although oral, synthetic androgens (e.g., methyltestosterone) are absorbed into the entero-hepatic circulation and adversely affect the liver, the same has not been shown with physiological bioidentical testosterone. Only a very small amount of testosterone is normally converted to estradiol, so the small physiologic oral dose required in women (2 mg) should not result in an excess of estradiol in individuals with normal aromatase activity. Although not a preferred route of administration in my opinion, the oral route in women is not ruled out by science, although it would require monitoring estradiol and estrone levels as well as testosterone.


Will Testosterone Increase Aggressive Behavior in Females?

Testosterone therapy has been shown to decrease anxiety, irritability, and aggression. Yet the implication that such therapy in women will cause increased aggression and rage remains in the literature. The adverse effects have been seen with anabolic steroids, not with physiologic amounts of testosterone. Even supra-physiologic doses of IM Testosterone Undecanoate have not demonstrated increased aggressive behavior. Excessive testosterone may run the risk of causing such issues though, as testosterone is converted to estradiol, and there is considerable evidence that estrogens play a major role in aggression and hostility in women.


Addressing Elevated Androgens & Breast Cancer Risk

Some epidemiological studies have reported an association between elevated androgens and breast cancer. However, these studies do not account for associated elevated estradiol levels and increased lean mass index. The “cause and effect” interpretation of these studies conflicts with the known biology of testosterone’s effect at the androgen receptor. Androgen receptor signaling exerts a pro-apoptotic, anti-estrogenic, growth inhibiting effect in both normal and cancerous breast tissue. Testosterone in fact is breast protective and does not increase the risk of breast cancer. It decreases breast proliferation and prevents stimulation from estradiol.


Synthetic Analogs & Supraphysiologic Dosing

Many of the side effects and safety concerns attributed to Testosterone are from the use of synthetic analogs and supra-physiologic dosing, or are secondary to increased aromatase activity, subsequent elevated estradiol levels and the effects at the estrogen receptor. Monitoring aromatase activity and estradiol and estrone levels is critical to the safe use of Testosterone in both sexes. Because of the many excellent review articles on the safety and long-term data, it can be concluded that the safety of physiologic testosterone replacement, especially non-oral, in women is well establish. Abandoning the myths, misconceptions, and unfounded concerns about testosterone and testosterone therapy in women will enable the practitioner to provide evidence based therapy.


Related Reading: How to Test for a Female’s Hormone Needs


Jim Paoletti, Dir of Education

Jim Paoletti, BS Pharmacy, FAARFM, FIACP, is the Director of Education at Power2Practice and a Clinical Consultant with over 30 years of experience creating and using bio-identical hormone therapies in both retail pharmacy and clinical practice.

Jim is a Diplomat in Functional Medicine in addition to being a former faculty member for the Fellowship of Functional Medicine. Jim is also author of the book “A Practitioner’s Guide to Physiologic Bioidentical Hormone Balance.”

At Power2Practice, he applies his wealth of knowledge and experience by hosting live webinars and creating useful content, such as blogs, podcasts and clinical support tools.


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