Human follicle stimulating hormone (hFSH) is a gonadotropin hormone involved in maturation of ovarian follicles and estrogen production in females and spermatogenesis in males. Its release is regulated via the hypothalamic-pituitary-gonadal axis. Proper regulation and function of hFSH in females is necessary for fertility, so its activity has been a focus in female fertility treatments and contraception. The hFSH receptor (hFSHR) is a GPCR found in granulosa cells in females and Sertoli cells in males and is responsible for initiating a complex downstream signaling cascade in both cell types. It has recently been discovered that hFSHR is capable of biased signaling, meaning it may be possible to selectively activate some downstream signaling pathways without affecting others. This biased signaling may be achieved through the addition of negative allosteric modulators (NAM’s), notably the small molecules ADX68692 and ADX68693, which bind to hFSHR and alter the receptors conformation. Both NAM’s have been shown to decrease FSH-dependent ovulation in vivo although have differing effects on steroid hormone production. The specific molecular mechanisms by which this occurs is unclear. Utilizing the human granulosa cell line hGrC1 we have observed differences in p44/42 MAPK signaling after treatment with NAM’s. In control conditions, activation of p42/44 MAP kinase peaked five minutes following FSH stimulation, but in the presence of NAM’s there was a continuous increase in signaling over thirty minutes. Additionally, signaling through protein kinase A (PKA) in the presence of ADX68692 showed increased activation of some substrates but in the presence of ADX68693 basal levels of the same substrates were initially higher and showed a decrease over time. Interestingly, some PKA substrates showed no difference in hFSH activation between untreated and NAM treated samples. The effects of treatment with NAM’s show their applicability in the development of novel non-steroidal contraceptive methods that could be associated with fewer side effects. Studying the complex biased signaling mechanisms of hFSHR could identify ways to manipulate hFSHR for not only improved methods of contraception but also fertility treatments.