Spironolactone was studied in adult women with persistent facial acne. Metformin was studied in women with hormonal or metabolic conditions, bicalutamide was studied in few women, and men were not studied.
Persistent acne means facial breakouts lasting at least six months into adulthood. A 2026 review described a shift beyond isotretinoin toward narrow-spectrum antibiotics, hormonal agents like spironolactone, and metabolic agents. According to Dermatology Times, the review found strong efficacy for spironolactone in adult women in the 2026 systemic therapy review.
Medical information disclaimer: This article is for general educational purposes only and does not provide medical advice, diagnosis, or treatment. Always consult a physician or other qualified health professional about symptoms, medications, tests, or treatment decisions.
Table of Contents
- Why look beyond isotretinoin?
- Who was studied with spironolactone?
- What do we know about metformin and bicalutamide?
- Who was left out and what should you discuss?
Why look beyond isotretinoin?
The review pointed to narrow-spectrum antibiotics, hormonal agents like spironolactone, and metabolic agents as alternatives to isotretinoin. Safety concerns and monitoring burden drove that shift.
Spironolactone showed strong efficacy in adult women and could outperform doxycycline. Combined oral contraceptives approached antibiotic efficacy by six months but carried thromboembolic risk. Thromboembolic risk means blood clots that can block vessels.
Who was studied with spironolactone?
According to the BMJ, the SAFA trial enrolled women age 18 and older in England and Wales in the SAFA trial report. All had facial acne for at least six months, with a mean age of 29.2 years.
Researchers randomized participants to spironolactone versus placebo. The trial excluded people with prior spironolactone use and kidney disease. It also excluded people planning pregnancy within six months and enrolled only women.
What do we know about metformin and bicalutamide?
Metformin was studied mainly in women with polycystic ovary syndrome or insulin resistance. In those studies it lowered IGF-1 and androgen signaling and improved acne scores. IGF-1 and androgens are natural signals that can raise oil and breakouts. These results do not cover unselected adults with persistent acne.
A reader without those conditions will not see herself in this data. Bicalutamide has only small observational data and no large acne trial. A 2020 Spanish series followed 44 women taking 25 to 50 mg daily for hair loss. Acne, oily skin, and excess hair were secondary observations, not the main study goal.
Who was left out and what should you discuss?
Men, pregnant patients, and children with persistent acne were not studied in SAFA. People with kidney disease or planned pregnancy within six months were also excluded. That leaves a gap for adults who need acne care during pregnancy or for male acne. Spironolactone has no FDA indication for acne and is used off-label. Its labeling warns of high potassium, kidney effects, and feminization of male fetuses in animal studies. There are no adequate human pregnancy studies.
Bicalutamide is approved only for prostate cancer and is not indicated for women. According to the U.S. National Library of Medicine DailyMed, it is barred in pregnancy and can injure the liver in the current bicalutamide label. Fetal harm drove the pregnancy ban, and liver risk requires monitoring. Write down when breakouts started, what you have tried, and other health conditions. Take that list plus your pregnancy plans and kidney history to your dermatology visit.
- Tell your clinician about kidney disease, prior spironolactone use, and pregnancy plans within six months.
- Mention a polycystic ovary syndrome or insulin-resistance diagnosis, since metformin data center there.
- Ask about potassium and kidney checks for spironolactone and liver checks for bicalutamide.
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