Lutropin alfa: a guide to its use in female infertility
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Lutropin alfa: a guide to its use in female infertility Adapted from Drugs 2008; 68 (11): 1529-40[1]
What is the rationale for developing the drug? Infertility in females is often caused by anovulation.[1] One cause of anovulation may be hypogonadotropic hypogonadism, which is a rare condition characterized by reduced hypothalamic or pituitary activity resulting in abnormally low serum levels of gonadotropins (folliclestimulating hormone [FSH] and luteinizing hormone [LH]), and negligible estrogen activity.[1] These women are amenorrhoeic, have no evidence of endogenous estrogen production, have non-elevated prolactin levels, normal or low FSH levels and no detectable spaceoccupying lesion.[1] Gonadotropin-releasing hormone (GnRH) agonists have been used off-label to treat hypogonadotropic hypogonadal women with intact pituitary function, as it restores the periodic release of both FSH and LH. Daily injections of gonadotropins are an alternative treatment in patients with pituitary disease or who do not respond adequately to treatment.[1] The offlabel use of human menopausal gonadotropin (hMG) [a urinary extract containing FSH and LH] has several limitations as an ovarian stimulant in this patient population, including an inherent variability in LH content, making it difficult to control the LH dose being administered.[1] There is a need, therefore, for the development of LH formulations with consistent hormone content, thereby providing the possibility of precise control of LH activity in patients who require LH therapy. Lutropin alfa (Luveris®) is the first and only currently available recombinant human form of LH.[1] Adis Evaluation Key clinical benefits and limitations of lutropin alfa in stimulating follicular development in infertile hypogonadotropic hypogonadal women Clinical benefits Provides consistent hormone content Promotes optimal follicular development Generally well tolerated Allows individual tailoring of the stimulation protocol Limitations Definitive effect on pregnancy has not yet been established
How does the drug work? LH belongs to a family of heterodimeric glycoprotein hormones including FSH, human chorionic gonadotropin (hCG) and thyroid-stimulating hormone, each with a unique β-subunit that confers physiological specificity.[2] LH binds rapidly and reversibly to a receptor that also binds hCG and is expressed on the granulosa and theca cells.[2] In the ovaries, during the follicular phase, LH stimulates the theca cells to produce androgens, which are converted by the granulosa cell aromatase enzyme to estradiol, which, in turn, supports FSH-induced follicular development.[3,4] At mid-cycle, ovulation and corpus luteum formation are triggered by high levels of LH, followed by progesterone production in the corpus luteum.[4] Furthermore, during later stages of follicle development, granulosa cells also express LH receptors and become receptive to LH stimulation.[5] Consequently, LH can influence both the theca and granulosa cells, and exert virtually all the physiological actions of FSH.[5]
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