Pharmacology of Progestins and Antiprogestins

Progestogens in general are a class of steroid hormones that bind to and activate the progesterone receptor. Progestins are a group of synthetic progestogens that have similar effects to those of natural progesterone. Once they’re inside the cells, they bind to progesterone receptors found in the cytoplasm, and together they form a complex that can travel into the nucleus and bind to progesterone-related genes, modifying the gene expression.

The Physiological Role of Progesterone

The hypothalamus secretes gonadotropin-releasing hormone, or GnRH, which travels to the nearby pituitary gland and stimulates it to secrete two hormones, follicle stimulating hormone, or FSH, and luteinizing hormone, or LH. During the two weeks following ovulation, which is referred to as the ovarian luteal phase, the remnant of the ovarian follicle becomes the corpus luteum, which is made up of luteinized theca and granulosa cells. These cells have been exposed to the high luteinizing hormone levels that occur just before ovulation. The luteinized cells secrete more progesterone than estrogen and progesterone becomes the dominant hormone.

Under the influence of progesterone, the uterus enters into the secretory phase of the endometrial cycle. During this time, spiral arteries continue to grow, and the endometrial glands continue to produce more secretions that make the endometrium more receptive to the implantation of a fertilized gamete. After day 15 of the cycle, the optimal window for fertilization begins to close and the corpus luteum gradually degenerates into the nonfunctional corpus albicans. The corpus albicans doesn’t make hormones, so estrogen and progesterone levels slowly decrease. When progesterone reaches its lowest level, the spiral arteries collapse and the functional layer of the endometrium prepares to shed during menstruation. This shedding marks the beginning of a new menstrual cycle and another opportunity for fertilization.

Apart from the female sex organs, progesterone also plays a role in bone strength, as well as keeping the skin elastic. Also, during pregnancy, the placenta takes over progesterone secretion, which is required to maintain the pregnancy and also helps prepare the breasts for lactation after delivery. But after menopause, the ovaries run out of functional ovarian follicles, which accounts for many of the symptoms preceding menopause, like hot flashes, night sweats, vaginal atrophy, and osteoporosis.

Classification of Synthetic Progestins

Synthetic progestogens, which are also called progestins, are divided into two groups: the progesterone derivatives and the testosterone derivatives. The progesterone derivatives include medroxyprogesterone, hydroxyprogesterone, and megestrol acetate. Now, the testosterone derivatives are basically derivatives of 19-nortestosterone and differ primarily in the degree of androgenic effects.

• Older testosterone derivatives: These include danazol, norgestrel, levonorgestrel, and ethynodiol, which are more androgenic.
• Newer testosterone derivatives: These include desogestrel, norgestimate, and etonogestrel.

Clinical Indications and Effects

Progestins are mainly used as contraceptives, in hormone replacement therapy, or HRT, and in the treatment of various gynecologic conditions. In general, they decrease growth and increase vascularization of the endometrium, and also thickens the cervical mucus. While they are able to stabilize the endometrium, they can’t support pregnancy effectively like endogenous progesterone does.

Antiprogestins

Antiprogestins act as progesterone antagonists and include mifepristone and ulipristal. Mifepristone is used for medical abortion while ulipristal is used as an emergency contraceptive.

Classification Summary