Parke davis div warner lambert co, Barr laboratories inc, Glenmark generics ltd, Ortho mcneil janssen pharmaceuticals inc, Watson laboratories inc, Duramed research inc, Glenmark generics ltd india, Warner Chilcott • Norethisterone is indicated as an oral contraceptive when given as monotherapy or in combination with an estrogen component, such as ethinylestradiol or estradiol. In combination with an estrogen component, oral norethisterone is also indicated as a hormone replacement therapy in the treatment of postmenopausal osteoporosis and moderate-to-severe vasomotor symptoms arising from menopause. When applied via transdermal patch, the combination of norethisterone and estradiol is indicated for the treatment of hypoestrogenism, vulvovaginal atrophy, and moderate-severe vasomotor symptoms. Norethisterone, taken in combination with intramuscular leuprolide, is also indicated for the symptomatic treatment of endometriosis-related pain.
Norethisterone is a synthetic second-generation progestin used for contraception, prevention of endometrial hyperplasia in hormone replacement therapy, and in the treatment of other hormone-mediated illnesses such as endometriosis.
On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development. When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies. Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes).
