Megestrol acetate

Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth. Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth. Side effects of MGA include increased appetite, weight gain, vaginal bleeding, nausea, edema, low sex hormone levels, sexual dysfunction, osteoporosis, cardiovascular complications, glucocorticoid effects, and others. MGA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak partial androgenic activity, weak glucocorticoid activity, and no other important hormonal activity. Due to its progestogenic activity, MGA has antigonadotropic effects. The mechanism of action of the appetite stimulant effects of MGA is unknown. MGA was discovered in 1959 and was introduced for medical use, specifically in birth control pills, in 1963. It may be considered a 'first-generation' progestin. The medication was withdrawn in some countries in 1970 due to concerns about mammary toxicity observed in dogs, but this turned out not to apply to humans. MGA was approved for the treatment of endometrial cancer in 1971 and wasting syndromes in 1993. It is marketed widely throughout the world. It is available as a generic medication. MGA is used mainly as an appetite stimulant to promote weight gain in a variety of situations. When given at very high dosages, it can substantially increase appetite in most individuals, even those with advanced cancer, and is often used to boost appetite and induce weight gain in patients with cancer or HIV/AIDS-associated cachexia. In addition to its effects on appetite, MGA appears to have antiemetic effects. MGA is also used as an antineoplastic agent in the treatment of breast cancer and endometrial cancer. It is significantly inferior to aromatase inhibitors in both clinical effectiveness and tolerability as a second-line therapy for breast cancer after tamoxifen failure. MGA was formerly used in combined oral contraceptives in combination with ethinylestradiol or mestranol, and has been used in a combined injectable contraceptive in combination with estradiol as well. Although it has not been approved for these uses, MGA has been studied and/or used off-label for a variety of indications including menopausal hormone therapy and the treatment of hot flashes, gynecological/menstrual disorders, endometriosis, endometrial hyperplasia, ovarian cancer, prostate cancer, benign prostatic hyperplasia, male breast cancer, and precocious puberty. Appetite stimulation is achieved with MGA with oral dosages of 400 to 800 mg/day. The optimal dosage with maximum effect for appetite stimulation has been determined to be 800 mg/day. The recommended oral dosage of MGA for breast cancer is 40 mg four times per day (160 mg/day total), while the medication is used at an oral dosage of 40 to 320 mg/day in divided doses for endometrial cancer. It has been used at far lower dosages (e.g., 1–5 mg/day oral, 25 mg/month i.m.) in combination with an estrogen for contraceptive purposes. MGA is available as 5 mg, 20 mg, and 40 mg oral tablets and in oral suspensions of 40 mg/mL, 125 mg/mL, 625 mg/5 mL, and 820 mg/20 mL. It was used at doses of 1 mg, 2 mg, 4 mg, and 5 mg in combined oral contraceptives. MGA is formulated at a dose of 25 mg in combination with a dose of 3.75 mg estradiol in a microcrystalline aqueous suspension for use as a once-monthly combined injectable contraceptive in women. Contraindications of MGA include hypersensitivity to MGA or any component of its formulation, known or suspected pregnancy, and breastfeeding. MGA is a teratogen in animals and may have the potential to cause fetal harm, such as decreased fetal weight and feminization of male fetuses. The most common side effect of MGA is weight gain, with an incidence of 15 to 70% at the high dosages used to treat breast cancer. Other side effects include vaginal bleeding (7–8%), nausea (7%), and edema (5%), as well as others such as dizziness and shortness of breath. MGA can cause hypogonadism and associated symptoms like diminished secondary sexual characteristics, sexual dysfunction, osteoporosis, and reversible infertility in men and premenopausal women. Combining MGA with an androgen/anabolic steroid like oxandrolone, nandrolone decanoate, or testosterone in men can alleviate MGA-associated symptoms of hypoandrogenism as well as further increase appetite and weight gain. Less common but more serious side effects of MGA include cardiovascular/thromboembolic complications such as thrombophlebitis. It may also cause glucocorticoid side effects such as Cushing syndrome-like symptoms, steroid diabetes, and adrenal insufficiency at high dosages. Case reports of deep vein thrombosis, pulmonary embolism, jaundice, intrahepatic cholestasis, and meningiomas in association with high-dosage MGA have been published.