Gonadotropin-releasing hormone (GnRH) analogues
This group includes synthetic polypeptides such as gonadorelin, buserelin, triptorelin, and goserelin. Their pharmacodynamics strictly depends on the administration regimen and is biphasic in nature.
- Stimulation phase. Occurs with single or pulsatile administration. The drug binds to adenohypophyseal membrane receptors, leading to the intracellular accumulation of diacylglycerol and inositol 1,4,5-trisphosphate. As a result, gonadotropins (FSH and LH) are released, and sex hormone levels (estrogens, gestagens, testosterone) rise.
- Depression phase. Develops with prolonged and continuous entry 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 decrease 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 (administered 3 times a day), subcutaneous depot capsules and microcapsule suspensions (administered once every 28 days), as well as biodegradable implants (lasting more than 2 months). The main indications include endometriosis, uterine myoma, 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 Leydig interstitial cells, enhancing testosterone production. It is used for anovulatory infertility, miscarriage, 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 created by genetic engineering. Differs by higher activity compared to menopausal gonadotropins. Actively stimulates follicular maturation and endometrial proliferation. Widely used for superovulation induction in ART programs.
Antiestrogens and the feedback principle
Normally, the production of endogenous GnRH and gonadotropins is regulated by estrogen and gestagen receptors via a negative feedback mechanism: high levels of sex hormones inhibit the activity of the hypothalamic-pituitary system.
To activate gonadotropic function, antiestrogenic agents are used. They cross the blood-brain barrier and block estrogen receptors. The body stops responding to estrogens, negative feedback is turned off, and the pituitary gland begins to actively secrete releasing factors and gonadotropins.
Safety profile and limitations
Therapy with gonadotropic drugs requires strict monitoring due to serious side effects.
- GnRH analogues can cause mood 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 cysts, as well as multiple or ectopic pregnancy. In men, 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.
The biphasic action of GnRH analogues is easy to remember through rhythm: "pulsatile" administration is life and stimulation (as normal), while "monotonous" continuous administration is receptor desensitization and medical "castration".
Class and exam questions
Why are GnRH analogues used to treat hormone-dependent tumors?
With prolonged continuous administration, they cause desensitization of pituitary receptors. This reduces sex hormone levels to postcastration values, depriving the tumor of growth stimulus.
How do antiestrogens enhance gonadotropin production?
They cross the BBB and block estrogen receptors of the hypothalamic-pituitary system. This removes the negative feedback effect, forcing the pituitary gland to produce more stimulating hormones.
What is the difference between follitropin beta and menotropins?
Menotropins are obtained from the urine of postmenopausal women and contain equal parts of FSH and LH. Follitropin beta is a recombinant drug produced by genetic engineering, possessing higher activity.
What else to study on this topic
- Development mechanisms and stages of ovarian hyperstimulation syndrome (OHSS)
- Gonadotropin application regimens in IVF and ART protocols
- Pharmacokinetics of various depot forms (microcapsules, implants)
- Treatment of hypogonadism of hypothalamic-pituitary origin in men
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