Testosterone undecanoate and hair: the risk of androgenic baldness

Androgenetic alopecia is the most common cause of hair loss in men, and testosterone plays a central role in it. That is why patients prescribed testosterone undecanoate often ask: "Will I go bald?" The answer depends on genetics, the hormone level and its conversion to DHT. The editorial team explains the mechanism and describes what is known about the real risks.

How androgens control hair growth

The effect of androgens on hair is paradoxical. On the face, chest and body they stimulate the transformation of thin vellus hair into thick and pigmented hair. But on the crown and in the frontal areas of genetically predisposed people, the same hormones gradually shrink the follicles, and the hair becomes thinner and shorter.

The key role is played by dihydrotestosterone (DHT), which is formed from testosterone under the action of type 2 5α-reductase, active in the hair follicles of the scalp. DHT binds to androgen receptors in the cells of the dermal papilla and changes the signals that control the hair growth cycle.

The classic observation by Hamilton (1942) showed that men castrated before puberty do not go bald; and administering testosterone to men predisposed to baldness triggered the process. It was later found that men with a congenital deficiency of type 2 5α-reductase also do not have androgenetic alopecia. These facts formed the basis of the modern understanding of the disease.

However, androgens alone are not enough: a genetic predisposition is needed. Most men have a normal level of testosterone, but baldness does not develop in everyone. Heredity is polygenic in nature, and one of the most well-known factors is variants of the androgen receptor gene, located on the X chromosome.

Follicle miniaturization: what happens in the skin

A hair grows cyclically. The growth phase (anagen) on the scalp lasts for years, followed by a short transitional phase (catagen) and a resting phase (telogen), when the hair falls out and the follicle prepares for a new cycle. Normally, most of the hair on the head is in anagen.

In androgenetic alopecia, under the influence of DHT, the anagen phase shortens with each cycle, and the follicle itself shrinks — miniaturization occurs. New hair becomes thinner, lighter and shorter, until it turns into barely noticeable fuzz. Outwardly this looks like gradual thinning.

The process usually follows a typical pattern: recession of the hairline at the temples and thinning at the crown. To assess the degree, the Norwood (Hamilton–Norwood) classification is used, which describes stages from barely noticeable changes to complete baldness of the upper part of the head.

It is important that miniaturization is a gradual process and, in the early stages, partially reversible. A follicle that has not yet lost the ability to produce hair may respond to treatment. On the other hand, completely atrophied follicles cannot be restored with medication.

Replacement therapy with undecanoate: does the risk increase

Testosterone undecanoate, after hydrolysis of the ester, yields ordinary testosterone, part of which is converted into DHT in the follicles. If a person has a genetic predisposition to baldness, any increase in the level of androgens can theoretically accelerate the process — primarily in those who had a pronounced deficiency before treatment.

At the same time, the goal of replacement therapy is to return the hormone level to the physiological range, that is, to the state in which millions of men without therapy exist. There are few high-quality randomized studies aimed specifically at assessing alopecia during testosterone therapy, and in clinical guidelines baldness is not considered a contraindication.

In practice, patients describe different things: some notice no changes, others note increased growth of body and beard hair, and in some predisposed people the rate of thinning on the head increases. The instructions for testosterone drugs mention alopecia and increased body hair growth among the possible adverse reactions.

Supraphysiological doses and drug combinations

With non-medical use of high doses of testosterone, there is much more substrate for 5α-reductase, and the level of DHT in tissues rises accordingly. In genetically predisposed people this can noticeably accelerate baldness: a process that would take decades unfolds in a much shorter time.

The risk is even higher when testosterone is combined with androgens that are DHT derivatives or that themselves have a strong androgenic effect. Such substances affect the follicle directly, and drugs that block 5α-reductase do not protect against their effect.

The Endocrine Society review (Pope et al., 2014) attributes accelerated male-pattern baldness to the typical androgenic side effects in users of anabolic steroids. For women who use androgens, baldness is often combined with a deepening of the voice and hirsutism, and some of these changes are irreversible.

It is also important to remember that hair lost as a result of miniaturization does not necessarily recover after drugs are discontinued. If the follicles have already atrophied, further thinning can be stopped, but returning what was lost is mostly possible only surgically.

Diagnosis and evidence-based treatment

Before starting testosterone therapy, it is useful to assess the state of the hair: a family history of baldness, existing signs of thinning, a "before" photo for later comparison. A dermatologist or trichologist can perform trichoscopy and determine the degree of miniaturization.

It is also worth ruling out other causes of hair loss that may coincide in time with the start of therapy: iron deficiency, thyroid dysfunction, stress, sharp weight loss, strict diets. Such conditions cause diffuse loss (telogen effluvium), which has a different mechanism and is often reversible.

The evidence base for treating androgenetic alopecia in men concerns primarily two approaches: topical minoxidil and 5α-reductase inhibitors. Finasteride in the study by Kaufman et al. (1998) slowed the progression of baldness and in some men improved hair density. Drugs of this group are prescription-only, have their own side effects and affect the PSA level, so they are prescribed by a doctor.

• assessment of family history and photo documentation before the start of therapy;
• trichoscopy at a dermatologist at the first signs of thinning;
• tests for ferritin, TSH to rule out other causes;
• discussing treatment options with a doctor before thinning becomes pronounced.

In the late stages, when the follicles are atrophied, the most effective method remains hair transplantation. It does not eliminate the need to control the process with medication, since the non-transplanted areas continue to respond to androgens.

Editorial conclusions

Androgenetic alopecia develops with a combination of two conditions: a genetic predisposition and the action of DHT on the hair follicles. Testosterone undecanoate, like any source of testosterone, provides substrate for the formation of DHT.

Within physiological replacement therapy, the risk of accelerated baldness exists, but mainly in predisposed people and usually moderate. Supraphysiological doses and combinations with strong androgens can significantly accelerate the process.

Early assessment of the state of the hair, ruling out other causes and timely evidence-based treatment help preserve hair even against the background of necessary hormonal therapy.

The editorial team also recommends familiarizing yourself with our materials on the effect of testosterone undecanoate on the skin and acne, on the psyche and on the kidneys.

References

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2. Norwood OT. Male pattern baldness: classification and incidence. South Med J. 1975;68(11):1359–1365.
3. Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4 Pt 1):578–589.
4. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
5. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
6. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.