The
gonadotropin receptors LH receptor and
FSH receptor play a central role in governing reproductive competency/fertility.
Gonadotropin hormone analogs have been used clinically for decades in assisted reproductive
therapies and in the treatment of various
infertility disorders. Though these treatments are effective, the clinical protocols demand multiple
injections, and the
hormone preparations can lack uniformity and stability. The past two decades have seen a drive to develop chimeric and modified
peptide analogs with more desirable pharmacokinetic profiles, with some displaying clinical efficacy, such as
corifollitropin alfa, which is now in clinical use. More recently, low-molecular-weight, orally active molecules with activity at
gonadotropin receptors have been developed. Some have excellent characteristics in animals and in human studies but have not reached the market-largely as a result of acquisitions by large pharma. Nonetheless, such molecules have the potential to mitigate risks currently associated with
gonadotropin-based fertility treatments, such as
ovarian hyperstimulation syndrome and the demands of injection-based
therapies. There is also scope for novel use beyond the current remit of
gonadotropin analogs in fertility treatments, including application as novel
contraceptives; in the treatment of
polycystic ovary syndrome; in the restoration of function to inactivating mutations of
gonadotropin receptors; in the treatment of ovarian and
prostate cancers; and in the prevention of bone loss and
weight gain in postmenopausal women. Here we review the properties and clinical application of current
gonadotropin preparations and their analogs, as well as the development of novel orally active, small-molecule nonpeptide analogs.