Gonadotropins and Their Analogues: Current and Potential Clinical Applications
The gonadotropin receptors, luteinising hormone receptor, and follicle-stimulating hormone receptor, play a central role in governing reproductive competency/fertility. Gonadotropin hormone analogues have been utilised clinically for decades, in assisted reproductive therapies, and in the treatment of various infertility disorders. While 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 analogues 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 due to 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 utilisation beyond the current remit of gonadotropin analogues in fertility treatments, including application as novel contraceptives, and in the treatment of polycystic ovary syndrome, the restoration of function to inactivating mutations of gonadotropin receptors, ovarian and prostate cancers, and in bone loss and weight gain in postmenopausal women.
Here, we review the properties and clinical application of current gonadotropin preparations and their analogues, as well as the development of novel orally-active small-molecule non-peptide analogues.
Anderson RC, Newton CL, Anderson RA, Millar RP. Gonadotropins and their analogues: current and potential clinical applications. Endocrine reviews 2018. Gonadotropins and their analogues: current and potential clinical applications | Endocrine Reviews | Oxford Academic
The gonadotropin receptors, luteinising hormone receptor, and follicle-stimulating hormone receptor, play a central role in governing reproductive competency/fertility. Gonadotropin hormone analogues have been utilised clinically for decades, in assisted reproductive therapies, and in the treatment of various infertility disorders. While 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 analogues 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 due to 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 utilisation beyond the current remit of gonadotropin analogues in fertility treatments, including application as novel contraceptives, and in the treatment of polycystic ovary syndrome, the restoration of function to inactivating mutations of gonadotropin receptors, ovarian and prostate cancers, and in bone loss and weight gain in postmenopausal women.
Here, we review the properties and clinical application of current gonadotropin preparations and their analogues, as well as the development of novel orally-active small-molecule non-peptide analogues.
Anderson RC, Newton CL, Anderson RA, Millar RP. Gonadotropins and their analogues: current and potential clinical applications. Endocrine reviews 2018. Gonadotropins and their analogues: current and potential clinical applications | Endocrine Reviews | Oxford Academic
