Progestin-only contraception

Historical background and evolution of the method

Hormonal contraception has come a long way in its development. As early as the beginning of the 20th century, Austrian researcher Haberlandt proved that ovarian extract could induce temporary sterilization. Between 1929 and 1934, estrogen and progesterone were discovered, followed by active attempts at their artificial synthesis.

The first contraceptive pill, Enovid, was created in the USA in 1960 by Pincus and co-authors. Since then, the development of pharmacology has followed the path of reducing estrogen doses and developing highly selective progestogens. This has significantly reduced the number of serious complications characteristic of first-generation drugs. Modern agents contain minimal doses of estrogens or consist exclusively of a progestogen component.

Classification and dosage forms

Hormonal contraceptives are divided into combined (containing estrogen and progestogen) and progestin-only. While combined agents are available as pills, vaginal rings, and patches, progestin-only contraception includes the following forms:

• Oral contraceptives with microdoses of progestogens. In clinical practice, they are widely known as mini-pills.
• Injectable preparations. Administered intramuscularly or subcutaneously, providing a prolonged effect.
• Implants. Inserted subcutaneously and gradually release the active substance into the systemic circulation.

Pharmacology of the progestogen component

Synthetic progestins (progestogens) are subdivided into two large groups depending on their chemical structure:

1. Progesterone derivatives. This group includes medroxyprogesterone, megestrol, and other compounds. Their main feature is that they are degraded by gastric juice. For this reason, when taken orally they do not produce a contraceptive effect and are used primarily for injectable contraception.
2. Nortestosterone derivatives (norsteroids). After absorption into the blood, these substances bind to progesterone receptors. It is important to note that the binding affinity and overall progestogenic activity of norsteroids are significantly higher than those of endogenous (the body's own) progesterone. In addition to their primary progestogenic action, norsteroids may exhibit varying degrees of androgenic, anabolic, and mineralocorticoid effects.

Norsteroid generations and their features

Nortestosterone derivatives are classified into generations, reflecting the evolution of their efficacy and safety:

• 1st generation: includes norethisterone, ethynodiol, and lynestrenol.
• 2nd generation: is characterized by greater activity; it includes norgestrel and levonorgestrel.
• 3rd generation: is represented by highly selective progestogens such as norgestimate, gestodene, desogestrel, dienogest, and drospirenone.

Third-generation drugs possess a number of unique pharmacological effects. They exert a pronounced anti-androgenic effect, which is due to two factors: an increase in the synthesis of sex hormone-binding globulin in the blood, and high selectivity (they bind predominantly to progesterone receptors while avoiding androgen receptors). In addition, drospirenone is characterized by a specific anti-mineralocorticoid action.

Mechanism of contraceptive action

Although maximum efficacy (Pearl index of 0.05–0.5) is reported for combined oral contraceptives, it is the progestogen component that is responsible for the key mechanisms of pregnancy prevention. The contraceptive effect is multifaceted and includes the following links:

• Suppression of ovulation: blockade of the cyclic processes of the hypothalamic-pituitary system occurs via negative feedback. There is also a direct inhibitory effect on the ovaries—follicle growth, development, and subsequent ovulation are absent.
• Cervical factor: progestogens significantly increase the viscosity of cervical mucus. It becomes thick and practically impassable for spermatozoa.
• Tubal factor: the progestogen component slows down the peristalsis of the fallopian tubes, which critically disrupts the progression of the ovum through them.
• Endometrial factor: the drugs cause regressive changes in the endometrium up to its complete atrophy. Even in the event of successful fertilization, implantation of the blastocyst into such a mucous membrane becomes impossible.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• History of the discovery of estrogen and progesterone in the first half of the 20th century
• Role and clinical significance of the ethinyl estradiol dose in combined preparations
• Classification of combined oral contraceptives by phasicity
• Simulation of a normal menstrual cycle when taking multiphasic drugs
• Complications and side effects associated with hormonal contraceptives

Other topics in the "Gynecology" section

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