Gonadotropin-Releasing Hormone (GnRH) Analogs
This group includes synthetic polypeptides such as gonadorelin, buserelin, triptorelin, and goserelin. Their pharmacodynamics strictly depend on the administration regimen and have a biphasic character.
- Stimulation phase. Occurs with single or pulsatile administration. The drug binds to adenohypophyseal membrane receptors, leading to intracellular accumulation of diacylglycerol and inositol 1,4,5-trisphosphate. As a result, gonadotropins (FSH and LH) are released, and sex hormone levels (estrogens, progestins, testosterone) rise.
- Suppression phase. Develops with prolonged and continuous delivery of the drug into the blood. Constant concentration causes desensitization (loss of sensitivity) of pituitary receptors. By the 14th day of therapy, FSH and LH secretion drops, and sex hormone levels fall to postcastration or postmenopausal values. This slows down the proliferation of hormone-dependent tissues.
To ensure a continuous effect, special dosage forms are used: nasal drops (used 3 times daily), subcutaneous depot capsules and microcapsule suspensions (administered once every 28 days), and biodegradable implants (effective for over 2 months). Main indications include endometriosis, uterine fibroids, hormone-dependent prostate cancer, and infertility treatment in IVF protocols.
Gonadotropin Preparations
These agents directly stimulate target organs (ovaries and testes).
- Chorionic Gonadotropin (Chorionic Gonadotropin). A natural hormone obtained from the urine of pregnant women. In women, it triggers ovulation and the synthesis of progesterone and estrogens, while in men, it stimulates interstitial Leydig cells, enhancing testosterone production. It is used for anovulatory infertility, recurrent pregnancy loss, as well as azoospermia and hypogonadism of hypothalamic-pituitary origin.
- Menotropins. Extracted from the urine of postmenopausal women. Contain natural pituitary hormones FSH and LH in equal proportions (75 IU each). In women, they induce follicular maturation; in men, spermatogenesis.
- Follitropin beta. Recombinant FSH produced by genetic engineering. It differs by having a higher activity compared to menopausal gonadotropins. It actively stimulates follicular maturation and endometrial proliferation. Widely used to induce superovulation in ART programs.
Antiestrogens and the Feedback Principle
Normally, the production of endogenous GnRH and gonadotropins is regulated by estrogen and progestin receptors via a negative feedback mechanism: high levels of sex hormones inhibit the hypothalamic-pituitary system.
To activate gonadotropic function, antiestrogen agents are used. They cross the blood-brain barrier and block estrogen receptors. The body stops responding to estrogens, negative feedback is disabled, and the pituitary gland begins actively secreting releasing factors and gonadotropins.
Safety Profile and Limitations
Gonadotropic drug therapy requires strict monitoring due to serious adverse effects.
- GnRH analogs can cause emotional lability, blood pressure instability, and hypersensitivity reactions. They are strictly contraindicated during pregnancy and lactation.
- Gonadotropins (especially menotropins and recombinant FSH) carry a high risk of ovarian hyperstimulation syndrome (OHSS), ovarian cyst formation, and multiple or ectopic pregnancies. In men, human chorionic gonadotropin can cause fluid retention, headaches, and depressive states.
- A general contraindication for stimulating drugs is the presence of hormone-dependent malignant neoplasms and pituitary tumors. For follitropin beta, additional contraindications include polycystic ovary syndrome (PCOS) and benign uterine tumors.