General adverse effects of HDE may include breast enlargement, breast pain and tenderness, nipple enlargement and hyperpigmentation, nausea and vomiting, headache, fluid retention, edema, melasma, hyperprolactinemia, galactorrhea, amenorrhea, reversible infertility, and others. More uncommon but serious side effects may include thrombus and thrombosis (e.g., venous thromboembolism), other cardiovascular events (e.g., myocardial infarction, stroke), prolactinoma, cholestatic jaundice, gallbladder disease, and gallstones. In women, HDE may cause amenorrhea and rarely endometrial hyperplasia or endometrial cancer, but the risk of adverse endometrial changes is minimized or offset with pseudopregnancy regimens due to the progestogen component. The tolerability profile of HDE is worse in men compared to women. Side effects of HDE specific to men may include gynecomastia (breast development), feminization and demasculinization in general (e.g., reduced body hair, decreased muscle mass and strength, feminine changes in fat mass and distribution, and reduced penile and testicular size), and sexual dysfunction (e.g., reduced libido and erectile dysfunction). The use of HDE in men has been associated with cellulite, which has been attributed to androgen deficiency.
High-dose estrogen
Nonsteroidal estrogen
Phytoprogestogen
Antiprogestogen
Male contraceptive
Phytoestrogen
Gestodene
Algestone