Testosterone Cypionate Acne: Supplements With the Best Evidence

Does testosterone cypionate cause acne?

Acne is listed in the Depo-Testosterone prescribing information among the skin reactions reported with some androgens, alongside seborrhea, hirsutism and male-pattern baldness [5]. The label's adverse reactions section lists acne without giving a frequency [5]. Acne is also described as one of the most common adverse effects of testosterone therapy for many transmasculine patients receiving it [8].

Zinc

A systematic review and meta-analysis of oral and topical zinc in acne found that people with acne had significantly lower serum zinc levels than controls, and that zinc-treated patients had a significant improvement in mean inflammatory papule count compared with those not treated with zinc; side-effect rates did not differ between zinc and comparators [6].

A multicenter trial enrolled 332 patients and compared 30 mg of elemental zinc daily with minocycline 100 mg daily for 3 months. Clinical success, defined as more than a two-thirds decrease in inflammatory lesions, was 31.2% on zinc and 63.4% on minocycline; minocycline was superior, and most adverse effects in both arms were moderate gastrointestinal complaints, with 5 dropouts on zinc and 4 on minocycline [1].

Nicotinamide (vitamin B3)

Topical nicotinamide has been tested as a non-antimicrobial alternative to clindamycin. A review of nicotinic acid and niacinamide notes that anti-inflammatory effects have been demonstrated in acne [9].

The key trial randomized 76 patients with moderate inflammatory acne to 4% nicotinamide gel or 1% clindamycin gel twice daily for 8 weeks. On physician global evaluation, 82% of the nicotinamide group and 68% of the clindamycin group improved, a difference that was not statistically significant (P=0.19). Papule and pustule counts fell 60% with nicotinamide and 43% with clindamycin (P=0.168), and acne severity fell 52% versus 38% (P=0.161) [4].

Note the form. The trial evidence is for a 4% gel applied to the skin, not for oral niacinamide capsules.

Omega-3 fatty acids

A 10-week randomized controlled trial assigned 45 people with mild to moderate acne to 2,000 mg of combined EPA and DHA daily, to a gamma-linolenic acid arm, or to a control group. After 10 weeks, inflammatory and non-inflammatory lesions decreased significantly in the supplemented groups, patient-rated improvement agreed, skin biopsies showed reduced inflammation and weaker interleukin-8 staining, and no severe adverse effect was reported [2].

That was a small trial with three arms, and it enrolled people with mild to moderate acne; it did not test acne during testosterone cypionate use [2]. The trial authors described omega-3 fatty acids as a possible adjuvant treatment [2].

Pantothenic acid (vitamin B5)

A randomized, double-blind, placebo-controlled trial tested a pantothenic acid-based dietary supplement in adults with mild to moderate facial acne. Forty-eight adults were enrolled and 41 were evaluable at 12 weeks. The pantothenic acid group had a significantly greater mean reduction in total lesion count than placebo (P=0.0197), a significantly greater reduction in inflammatory lesions, and better Dermatology Life Quality Index scores; the supplement was reported as safe and well tolerated, with complete blood counts and liver function measured [3].

The tested product was a pantothenic acid-based dietary supplement, not pantothenic acid alone, and the trial ran 12 weeks [3].

Green tea extract (EGCG)

EGCG, the main polyphenol in green tea, has both laboratory and clinical data. In cultured human sebocytes it reduced sebum through the AMPK-SREBP-1 pathway, suppressed NF-kB and AP-1 inflammatory signaling, and decreased the viability of P. acnes; in an 8-week randomized split-face clinical trial it significantly improved acne and was well tolerated [10]. The same paper notes that only isotretinoin and hormonal therapy reduce sebum production [10].

A separate randomized, double-blind trial gave 80 women aged 25 to 45 either 1,500 mg of decaffeinated green tea extract (856 mg EGCG) or placebo daily for 4 weeks; 64 completed. Inflammatory lesions on the nose, around the mouth and on the chin differed significantly between groups, but total lesion counts did not [11].

Probiotics

The probiotic evidence here is a 20-person pilot. It randomized adults with acne to Lactobacillus rhamnosus SP1 at 3 billion CFU per day or a placebo liquid for 12 weeks, 10 people per group. The probiotic group was far more likely to be rated improved or markedly improved by the investigator, with an adjusted odds ratio of 28.4 (95% CI 2.2 to 411.1, P<0.05), and skin expression of insulin-signaling genes changed in the probiotic group but not with placebo [12]. The confidence interval is very wide, reflecting the small sample.

Vitamin D

A study of 80 acne patients and 80 healthy controls found vitamin D deficiency in 48.8% of acne patients versus 22.5% of controls, and 25(OH)D levels were inversely associated with acne severity, particularly inflammatory lesions. In a follow-on trial, 39 acne patients with deficiency took 1,000 IU of cholecalciferol daily for 2 months and their inflammatory lesions improved; the authors listed the small number of patients in the supplementation study and the natural fluctuation of acne as limitations [7].

Excessive vitamin D intake can cause serious toxicity, with a 25(OH)D concentration above 150 ng/mL the hallmark of overdose from high-dose supplements [13]. The same review notes that toxicity can also arise from disorders of vitamin D metabolism or from disease that produces the active metabolite, and that hypercalcemia has appeared in some people taking doses considered safe [13].

DIM (diindolylmethane)

DIM (diindolylmethane) is the major bioactive indole in cruciferous vegetables. The review of DIM covers breast cancer chemoprevention, not skin disease [14].

How the options compare

In acne studies, zinc improved inflammatory papule counts in a meta-analysis [6] and omega-3 supplementation reduced lesions over 10 weeks in a 45-person trial [2]. A pantothenic acid-based supplement reduced total lesion count versus placebo over 12 weeks [3]. Oral green tea extract did not significantly change total lesion counts over 4 weeks [11], and the probiotic evidence is a 20-person pilot rated by investigator global improvement [12]. For severe or treatment-refractory acne, a practical guide to acne care in people receiving testosterone discusses isotretinoin and the iPLEDGE program that governs its prescribing [8].