The gonadotropins are peptide hormones that regulate ovarian and testicular function and are essential for normal growth, sexual development and reproduction. The human gonadotropins include follicle stimulating hormone (FSH) and luteinizing hormone (LH) which are made in the pituitary, and chorionic gonadotropin (hCG) which is made by the placenta. All three gonadotropins are heterodimeric proteins that consist of two peptide chains, the alpha chain is similar in all three, whereas the beta chain is unique and determines the fine receptor specificity and function of each hormone. The pituitary gonadotropins are under the control of gonadotropin releasing hormone (GnRH), a decapeptide produced in the hypothalamus and released in response to circulating levels of estrogens and progesterone. Highly purified and recombinant formulations of the gonadotropins have been developed and used in the treatment of hypogonadism and infertility. Synthetic forms of GnRH have been used with the gonadotropins in assisted reproductive techniques and in vitro fertilization. Therapeutic use of the gonadotropins and GnRH has not been linked to serum enzyme elevations or with clinically apparent liver injury. However, in high doses, the gonadotropins can induce the ovarian hyperstimulation syndrome (OHSS) which may be accompanied by liver test abnormalities, jaundice, edema and ascites.
Follicle stimulating hormone (FSH) is a pituitary hormone that regulates growth, sexual development and reproduction, including menstruation, follicular development and ovulation. FSH is regulated, at least in part, by GnRH produced in the hypothalamus in response to multiple signals including circulating levels of sex hormones. FSH interacts with receptors on ovarian follicles and is the major survival factor for the maturing follicles. A surge in FSH levels occurs in the middle of the menstrual cycle leading to ovulation. In men, FSH promotes spermatogenesis and androgen responsiveness in the testes. Thus, FSH is essential for sexual maturation and reproduction in both men and women. Partially and highly purified urinary derived FSH (menotropins, Menopur which also has LH activity; urofollitropin, Bravelle) and recombinant forms of FSH (follitropin alpha, Follistim, Gonal F) are available and approved for use in treatment of infertility and hypogonadism. They are generally given by subcutaneous injection daily or several times weekly. The dose and appropriate regimen vary by indication. These agents should be used only by health care workers with expertise in management of infertility and hypogonadism.
Luteinizing hormone (LH) is a pituitary hormone that is essential for sexual development and reproduction in both men and women. LH is regulated by GnRH from the hypothalamus which is sensitive to circulating levels of sex hormones. LH interacts with receptors on ovarian follicles and promotes their maturation. In the middle of the menstrual cycle, a surge of LH triggers ovulation and production of progesterone by the corpus luteum that is necessary for the maturation of the uterine endometrium for implantation of the fertilized egg. In males, LH stimulates production of testosterone by the testes. LH is used clinically in assisted reproduction techniques (ART) and in vitro fertilization (IVF) to stimulate ovarian follicle maturation. Both urinary derived (menotropin, Menopur, which also has FSH activity) and recombinant forms (lutropin alfa: Luveris) of human LH have been developed, but not all are available in the United States. LH is generally administered by subcutaneous injection in a cyclic and step-wise fashion. The dosages and regimens of administration vary by indication. These agents should be used only by health care workers with expertise in management of infertility and hypogonadism.
Human chorionic gonadotropin (kor" ee on' ik) (hCG) is a polypeptide hormone produced by the placenta following implantation of the fertilized egg. Circulating human chorionic gonadotropin interacts with the luteinizing hormone receptors of the ovary, promoting the corpus luteum and its production of progesterone which is necessary to maintain pregnancy and support the growth of the fetus. Injections of hCG mimic the surge in LH that is necessary for ovulation and are used in the therapy of female infertility, in assisted reproduction techniques. In clinical trials, hCG resulted in pregnancies in approximately 30% of women. hCG prepared from urine of pregnant women and was approved for use in the United States in 1967 as treatment of ovulatory dysfunction in women desiring pregnancy. Subsequently, recombinant forms of hCG have been developed and licensed for use. Currently, hCG is available as a powder or in solution generically and under trade names such as Novarel and Pregnyl. Recombinant hCG is available as Overle. The dose and regimen of hCG therapy varies by indication and it should be used only by physicians with expertise in the management of infertility and hypogonadism. Common side effects include headache, nausea, anorexia, and local injection reactions. Uncommon, but potentially severe adverse events include ovarian hyperstimulation syndrome.
Gonadotropin releasing hormone (GnRH) is a decapeptide, neurohormone produced in the hypothalamus and released in a pulsatile manner. GnRH acts on the pituitary leading to synthesis and secretion of LH and FSH. GnRH activity is low during childhood and increases markedly during puberty. The proper pulsatile activity of GnRH is necessary for reproduction, but once pregnancy is established it is no longer necessary, gonadotropin activity being assumed by chorionic gonadotropin produced by the placenta. Synthetic GnRH is used as a part of assisted reproductive techniques as a means of controlling ovarian overstimulation. GnRH is available in solution for injection and its use should be restricted to physicians with expertise in assisted reproductive techniques. In addition, several synthetic GnRH analogues and GnRH antagonists have been developed as therapy of various conditions including hormone-sensitive cancers (breast and prostate), endometriosis and precocious puberty. These products are discussed separately in LiverTox as gonadotropin releasing hormone agonists and antagonists.