Research

Peptides play a central role in fertility regulation, menstrual health, and gonadal signaling. One of the most significant discoveries in reproductive endocrinology is Kisspeptin, the hypothalamic peptide that triggers the hypothalamic–pituitary–gonadal (HPG) axis. It directly stimulates GnRH neurons, leading to luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release which are key steps for ovulation, spermatogenesis, and menstrual rhythm. Translational and human studies have shown that Kisspeptin can activate the HPG axis in both sexes and has been used to safely induce oocyte maturation in women undergoing IVF [1–3].

In conditions such as polycystic ovary syndrome (PCOS) and menstrual irregularities, altered Kisspeptin–LH signaling contributes to abnormal hormone pulsatility and androgen excess. Clinical and mechanistic work shows disrupted temporal coupling between Kisspeptin and LH pulses in PCOS, suggesting an important regulatory imbalance [4,5]. In the ovary itself, Follistatin, which binds and inhibits activins, influences follicle recruitment and steroidogenesis, positioning it as a target of interest for improving ovarian function and cycle regularity [6].

Metabolic peptides also indirectly affect reproductive health. Tesamorelin, a growth hormone–releasing hormone analogue, has demonstrated clinically significant reductions in visceral and hepatic fat, both of which are linked to insulin resistance, subfertility, and anovulatory cycles in women with metabolic disorders [7,8]. Together, these peptide systems provide an emerging model for how neuroendocrine, gonadal, and metabolic health intersect to shape fertility outcomes and hormonal balance across the lifespan.

References

1. Messager S, et al. Kisspeptin directly stimulates GnRH release via GPR54. Proc Natl Acad Sci U S A.2005;102(5):1761–1766. PMID: 15665093
2. Dhillo WS, et al. Kisspeptin-54 stimulates the hypothalamic–pituitary–gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609–6615. PMID: 16174713
3. Abbara A, et al. Efficacy of Kisspeptin-54 to trigger oocyte maturation in women undergoing IVF treatment. J Clin Endocrinol Metab. 2015;100(9):3322–3331. PMID: 26192876
4. Katulski K, et al. Kisspeptin and LH pulsatile temporal coupling in women with PCOS. Clin Endocrinol (Oxf).2018;88(5):744–752. PMID: 29728876
5. Katulski K, Podfigurna A, Czyzyk A, Meczekalski B, Genazzani AR. Kisspeptin and LH pulsatile temporal coupling in women with PCOS. Clinical Endocrinology (Oxf). 2018;88(5):744–752. PMID: 29728876
6. Knight PG, Glister C. TGF-β superfamily members and ovarian follicle development. Reproduction. 2006;132(2):191–206. PMID: 16885529
7. Stanley TL, Feldpausch MN, Oh J, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821–e830. PMID: 31611038