Antiandrogens like spironolactone are male-specific teratogens which can feminize male fetuses due to their antiandrogen effects (see below ).    For this reason, it is recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.    Oral contraceptives, which contain an estrogen and a progestin , are typically used for this purpose.  Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.  
Information from the Nurses' Health Study indicated that the combination of estrogen and androgen used to treat hypoandrogenism could increase breast cancer risk. However, other studies indicated androgens may decrease breast cancer risk. Follow-up studies on the Women's Health Initiative found women who received estrogen and no progestogen showed a significant decrease in cardiovascular disease (CVD) and breast cancer. This has caused a reconsideration of androgens added to estrogens. Still, the FDA requires demonstration of CVD and breast cancer safety for any product containing androgens or estrogen plus an androgen; that has not been done.
Neither ALDACTONE nor potassium canrenoate produced mutagenic effects in tests using bacteria or yeast . In the absence of metabolic activation, neither ALDACTONE nor potassium canrenoate has been shown to be mutagenic in mammalian tests in vitro . In the presence of metabolic activation, ALDACTONE has been reported to be negative in some mammalian mutagenicity tests in vitro and inconclusive (but slightly positive) for mutagenicity in other mammalian tests in vitro . In the presence of metabolic activation, potassium canrenoate has been reported to test positive for mutagenicity in some mammalian tests in vitro , inconclusive in others, and negative in still others.