Progestogens

Physiology and mechanism of action

Natural progesterone is synthesized in the ovaries (by the corpus luteum in the luteal phase), placenta, testes, and partially in the adrenal cortex. Its production is stimulated by luteinizing hormone (LH), the secretion of which is inhibited by progesterone itself via negative feedback.

The hormone penetrates the plasma membrane and binds to a cytosolic receptor. Chaperone proteins dissociate from the receptor, which is then phosphorylated and forms dimers. The complex enters the nucleus, binds to DNA, and triggers the transcription of specific genes.

Main physiological effects:

• Reproductive system: induces secretory transformation of the endometrium (preparation for implantation), thickens cervical mucus (barrier to spermatozoa), decreases myometrial tone (tocholytic effect), and stimulates the growth of glandular breast tissue.
• Metabolism: increases glycogen stores in the liver, stimulates insulin release, increases lipoprotein lipase activity (fat storage), and decreases sodium reabsorption by competing with aldosterone.

Classification of synthetic progestogens

Synthetic drugs are divided into three groups. Their most important feature is the ability to bind to "off-target" receptors (androgenic, estrogenic, mineralocorticoid), which determines the individual profile of the drug.

1. Progesterone derivatives. The introduction of a methyl group at the $C_6$ position increases their oral activity.
2. Representatives: medroxyprogesterone, megestrol, dydrogesterone, cyproterone.
3. Feature: cyproterone has a pronounced antiandrogenic effect.

1. 19-Nortestosterone derivatives. Characterized by the replacement of the methyl group at the $C_{19}$ position with hydrogen. The group is heterogeneous in its effects.
2. With an ethynyl radical: estrane derivatives (norethisterone — has estrogenic and androgenic effects) and gonane derivatives (levonorgestrel — has residual androgenic activity).
3. Without an ethynyl radical: dienogest (characterized by an antiandrogenic effect).

1. Spironolactone derivatives.
2. Representative: drospirenone.
3. Feature: the profile is as close as possible to natural progesterone. It has a potent antimineralocorticoid effect (prevents sodium and water retention).

Clinical application

Progestogens are used as monotherapy or in combination (most commonly with ethinylestradiol):

• Contraception: as a component of combined oral contraceptives (COCs). Levonorgestrel is used for emergency contraception (Postinor — 0.75 mg, taken twice at a 12-hour interval within 48–72 hours after intercourse).
• Hormone replacement therapy (HRT): added to estrogens to protect the endometrium from hyperplasia and cancer. However, a pronounced antiestrogenic effect of progestogen is undesirable here, as it neutralizes the benefits of estrogens (bone protection and improved lipid profile).
• Treatment of hyperandrogenism: COCs containing antiandrogenic progestogens (cyproterone, dienogest, drospirenone) are used for acne, hirsutism, and alopecia.
• Gynecological pathology: dydrogesterone is used for endocrine miscarriage. The levonorgestrel-releasing intrauterine system is effective for endometriosis and uterine fibroids.

Antiprogestogens

This is a group of substances that block the action of progesterone by competing for its receptors. The main representative is mifepristone (a 19-norethisterone derivative).

Indications for use (strictly under medical supervision):

1. Medical termination of pregnancy in the first trimester (single dose, followed 48 hours later by prostaglandins to expel the gestational sac).
2. Preparation for labor (for cervical ripening and dilation at term pregnancy).
3. Emergency contraception (by suppressing ovulation).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The role of heat shock proteins (chaperones) in progesterone receptor activation
• Comparative characteristics of estrane and gonane derivatives
• Effect of progestogens on carbohydrate and lipid metabolism: mechanisms of side effect development
• Use of transdermal progestogen formulations in benign breast diseases
• Regimens of mifepristone and prostaglandin use in medical abortion

Other topics in the section "Hormone preparations, their synthetic substitutes, and antagonists"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.