Testosterone isocaproate and skin: acne and oiliness

Testosterone isocaproate rarely appears as a standalone drug: mostly it is one of four esters in blends like “Sustanon 250.” However, from the skin’s point of view, what matters is not the label but how many androgens the sebaceous glands receive. The editorial team broke down why the skin becomes oily on testosterone esters, how acne develops, and when it stops being a cosmetic problem.

Isocaproate in drug formulations: what matters for the skin

Testosterone isocaproate is an ester of testosterone and isocaproic (4-methylpentanoic) acid with six carbon atoms in the chain. In terms of release duration it occupies an intermediate position between phenylpropionate and decanoate. In medical practice it is used mainly in combination drugs: in “Sustanon 250,” according to the instructions, 1 ml contains 60 mg of isocaproate alongside propionate, phenylpropionate and decanoate.

For the skin, the ester as such has almost no significance. After esterases cleave off the acid “tail,” ordinary testosterone enters the tissue. It and its metabolite dihydrotestosterone (DHT) affect the sebaceous glands, hair follicles and keratinocytes. That is why the skin effects of isocaproate in pure form have not been studied separately — they are extrapolated from data on testosterone in general.

Another point is practically important: blend drugs create a multiphase concentration curve, where the short propionate gives a rapid rise, while isocaproate and decanoate sustain the level longer. The skin reacts not to peak days but to total androgen exposure, so a rash often appears a few weeks after the start of administration and may persist for some time after discontinuation.

It should also be remembered that in commercial blends the oil base and excipients (for example, benzyl alcohol) can cause local reactions at the injection site. This is not acne but a separate problem — irritation or inflammation of the tissue, which is sometimes mistakenly perceived as a “rash from hormones.”

The sebaceous gland as a target of androgens

The sebaceous glands are among the structures most sensitive to androgens in the body. Their cells, sebocytes, contain androgen receptors and enzymes that convert testosterone into DHT, in particular type 1 5-alpha-reductase. DHT binds to the receptor more strongly than testosterone, so even a moderate rise in androgens noticeably enhances the glands’ activity.

Under the influence of androgens, sebocytes divide more often, and the glands increase in size. Both the amount of sebum increases and its composition changes. That is why the first sign people notice on testosterone esters is not pimples but an oily shine on the face, scalp, back and chest.

This dependence is well illustrated by physiology: in childhood, when there are few androgens, the sebaceous glands are almost inactive; at puberty they “switch on” together with the rise in testosterone. People with complete insensitivity to androgens have practically no acne. These are natural models that confirm the leading role of androgens.

Dermatologists identify several links through which androgens affect the skin:

• Seborrhea:increased sebum production.
• Duct hyperkeratosis:sticking together of cells at the mouth of the follicle and the formation of microcomedones.
• Microbial factor:proliferation ofCutibacterium acnesin a lipid-rich environment.
• Inflammation:the immune response to bacterial products and follicle rupture.

Genetics determine how strong the reaction will be. In a person who had severe acne in adolescence, the likelihood of the problem recurring on high doses of androgens is higher than in someone whose skin was calm in youth.

From oiliness to acne: how the process develops

The typical sequence is as follows: first the skin becomes oilier, then open and closed comedones appear, and later — inflammatory papules and pustules. The favorite locations of androgenic acne are the back, shoulders, chest and face. Involvement of the back is often more pronounced than the face, which distinguishes it from typical adolescent acne.

It is important that rashes often worsen after a sharp drop in androgen levels, not only at their peak. Fluctuations in the hormonal background, a change in the testosterone-to-estradiol ratio, stress and lack of sleep act as additional triggers, so the skin may “break out” precisely when a person expects improvement.

In athletes, acne is also affected by everyday factors: prolonged wearing of wet synthetic clothing, friction against exercise machines and backpacks, excessive sweating. They do not cause androgenic acne on their own, but they worsen the course of an already existing process.

Oiliness of the scalp is often accompanied by seborrheic dermatitis — flaking, itching, redness along the hairline and near the nose. This is a separate condition associated with yeast-like fungi of the genusMalassezia, which is promoted by an excess of sebum.

Severe forms and other skin reactions

The greatest concern among dermatologists is caused by the nodulocystic forms. A review by Melnik and colleagues (2007) called “bodybuilders’ acne” an underestimated problem: in users of anabolic steroids, cases ofacne conglobatawith deep confluent nodules andacne fulminans— a rare form with sudden ulceration, fever and joint pain — have been described.

Such forms leave atrophic and hypertrophic scars that do not disappear after stopping the drug. Treating scars is a long and expensive process, so an early visit to a dermatologist is more advantageous here than trying to “wait it out.”

Besides acne, on high doses of androgens striae — stretch marks on the shoulders, chest and armpit areas — often appear. They are associated with a rapid increase in muscle volume and the effect of hormones on connective tissue. Striae lighten over time but do not disappear completely.

There are also reports of increased body hair growth, hirsutism and virilization in women, boils and infections at injection sites. The latter are associated not with the hormone but with a breach of sterility — and can progress to abscesses that require surgical opening.

What a dermatologist does

First, the doctor determines the cause. A frank conversation about the use of androgens is essential here: without it, a dermatologist may treat “ordinary” acne for a long time, not understanding why the therapy does not work. The doctor also checks whether there are other causes of the rash — for example, steroid folliculitis from glucocorticoids or a reaction to iodine-containing supplements.

Basic therapy for mild and moderate acne is topical retinoids, benzoyl peroxide, azelaic acid, and if needed — a course of systemic antibiotics. The tactics are determined by the doctor depending on the severity, while self-treatment with antibiotics promotes bacterial resistance.

For severe nodulocystic forms, dermatologists consider systemic isotretinoin. It is an effective but serious drug with teratogenicity and effects on the liver and lipids, so it is prescribed only under regular laboratory monitoring. Combining isotretinoin with androgens additionally burdens the lipid profile and the liver, which the doctor necessarily takes into account.

The key factor of success is eliminating the cause. As long as androgen levels remain supraphysiological, any acne treatment works worse, and relapses occur more often. In most people the skin gradually normalizes within a few months after stopping the drugs, but scars remain forever.

Editorial conclusions

Testosterone isocaproate acts on the skin the same way as any other source of testosterone: through the androgen receptors of the sebaceous glands and conversion to DHT. The ester determines only how long the exposure lasts.

Oily skin is an almost inevitable effect of supraphysiological androgen levels, acne is common, and nodulocystic and fulminant forms are rare but capable of leaving scars for life.

If rashes have appeared, do not delay: a dermatologist will select treatment, and honest information about hormones will help avoid futile months of therapy.

The editorial team also advises reading our articles about the effect of testosterone isocaproate on hair and the risk of androgenic baldness, about the drug’s interaction with alcohol and medications, and about the body’s recovery after its use.

References

1. Melnik B, Jansen T, Grabbe S. Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem. J Dtsch Dermatol Ges. 2007;5(2):110–117.
2. 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.
3. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973.
4. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
5. Nieschlag E, Behre HM, Nieschlag S (eds). Testosterone: Action, Deficiency, Substitution. 4th ed. Cambridge University Press; 2012.
6. Sustanon 250 solution for injection. Summary of Product Characteristics. Electronic Medicines Compendium (UK).