The goal of this trial is to compare the effectiveness, safety and tolerability of spironolactone and doxycycline hyclate in the treatment of moderate to severe acne in women. Both medications are common treatments for acne, but it is not known how well they compare to one another.

Spironolactone was originally developed and approved by the Food and Drug Administration (FDA) as a potassium-sparing diuretic to treat high blood pressure, hyper aldosternism (excess production of the adrenal gland) and heart failure, but for many years it has also been used off-label in the treatment of acne. Doxycycline, a tetracycline-class drug, is FDA approved and commonly used to treat infections caused by certain bacteria. You will also have the option to opt-in to a study in which researchers will assess the impact of these treatments on the microbiome and the development of antibiotic resistance. Microbiome samples will be collected from your skin. To collect the samples research staff will swab an approximately 4 centimeter square area (2 by 2 centimeter square) of skin in up to 3 different places: on your face, behind your ear and your oropharynx (throat). The swabs will then be placed in a solution to be sent to the lab to look for microbes. If you agree to participate in this study your involvement will last up to 16 weeks (4 months). This study is being conducted at clinics across the United States.