Description

Norethisterone is a synthetic progestin (progestogen), a derivative of testosterone. It is an oral medication that acts similarly to the naturally occurring hormone progesterone. It is a highly active and versatile hormonal agent used for a wide range of gynecological and reproductive health purposes, often as a single agent or in combination with an estrogen.

Indication

Norethisterone is indicated for the treatment of various gynecological conditions and for contraception. Its main indications include:

• Abnormal Uterine Bleeding: To treat dysfunctional uterine bleeding (menorrhagia) by stabilizing the uterine lining.

• Endometriosis: To relieve the pain and other symptoms of endometriosis by creating a hormonal state that suppresses the growth of endometrial tissue outside the uterus.

• Dysmenorrhea: To treat severe or painful menstruation.
• Postponement of Menstruation: It can be used to delay the onset of a menstrual period for a short time, for convenience during events or travel.

• Hormone Replacement Therapy (HRT): In combination with an estrogen, it is used in postmenopausal women with an intact uterus to prevent endometrial hyperplasia and reduce the risk of endometrial cancer.

• Contraception: As a component of oral contraceptive pills (in combination with estrogen) or as a progestin-only pill.

Mechanism of Action

The therapeutic effects of Norethisterone are based on its ability to mimic the actions of natural progesterone by acting as a potent agonist at progesterone receptors.

1. Progesterone Receptor Agonism: Norethisterone binds with high affinity to progesterone receptors in the hypothalamus, pituitary gland, and reproductive organs (uterus, cervix, etc.). This binding initiates a series of physiological responses that are characteristic of progesterone.

2. Suppression of Gonadotropins: By acting on the hypothalamus and pituitary, norethisterone inhibits the release of gonadotropin-releasing hormone (GnRH), which in turn suppresses the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The suppression of the LH surge is particularly important, as it is required for ovulation. This is the primary mechanism for its contraceptive effect.
3. Endometrial Changes: Norethisterone has a profound effect on the endometrium (the uterine lining). It causes the endometrium to become thin, atrophic, and unsuitable for the implantation of a fertilized egg. This action is crucial for treating abnormal bleeding and for its contraceptive effect. In endometriosis, this action helps to suppress the growth of the ectopic endometrial tissue.
4. Cervical Mucus Alteration: It causes the cervical mucus to become thick and viscous, making it difficult for sperm to penetrate and travel to the egg.
5. Anti-Estrogenic Effects: Norethisterone also has anti-estrogenic effects, which is why it is effective in counteracting the proliferative effects of estrogen on the endometrium in HRT, thereby preventing hyperplasia and cancer.