Kisspeptin and neurokinin B — two neuropeptides that control reproduction — are being translated into clinical therapies for infertility, menopause symptoms, endometriosis, and uterine fibroids.
Master regulator of reproductionKisspeptin controls both puberty onset and adult fertility, and human studies confirm it can stimulate reproductive hormones in healthy people and patients with disorders
What the researchers found
Kisspeptin has been established as the master regulator of mammalian reproduction, controlling both puberty onset and ongoing fertility. Human studies confirm that kisspeptin administration stimulates physiological reproductive hormone secretion in healthy men and women, as well as in patients with common reproductive disorders.
Neurokinin B (NKB), which works alongside kisspeptin in KNDy neurons (kisspeptin/neurokinin B/dynorphin neurons), has emerged as a therapeutic target for menopausal hot flashes, endometriosis, and uterine fibroids. NKB receptor antagonists are being developed as treatments for these conditions. Together, kisspeptin and NKB represent two complementary peptide-based approaches to managing reproductive health.
Why it matters
Current fertility treatments rely heavily on synthetic GnRH analogs and gonadotropin injections, which can cause side effects like ovarian hyperstimulation syndrome. Kisspeptin offers a more physiological alternative that stimulates the body's own hormone cascade. Meanwhile, NKB antagonists are already reaching late-stage clinical trials for menopause symptoms and gynecological conditions, positioning these reproductive neuropeptides as the basis for an entirely new class of therapies.
How the study worked
This is an invited narrative review synthesizing evidence from animal models, human physiological studies, and clinical trials involving kisspeptin and neurokinin B in reproductive health contexts.
What this study cannot tell us
As a narrative review, this paper summarizes and interprets existing evidence rather than presenting new experimental data. The review focuses on kisspeptin and NKB while noting that dynorphin (the third KNDy peptide) also plays important roles that are less therapeutically developed. Some of the clinical applications discussed were still in early-stage trials at the time of writing.
How to read the evidence
This is an invited review article synthesizing evidence from animal studies, human physiological experiments, and clinical trials. It provides a comprehensive overview rather than new primary data, but the reviewed evidence includes human clinical studies.
When this study was published
Published in 2022, this review captures the state of kisspeptin and NKB therapeutics development. Since then, NKB antagonists like fezolinetant have gained regulatory approval, validating the therapeutic direction described here.
The bigger picture
The discovery of kisspeptin's role in reproduction (around 2003) reshaped reproductive endocrinology. NKB antagonists like fezolinetant have since reached clinical approval for menopausal vasomotor symptoms, validating the therapeutic potential of targeting the KNDy neuron system. Kisspeptin-based IVF triggers are being studied as safer alternatives to hCG, which can cause dangerous ovarian hyperstimulation. This review captures a pivotal moment when basic neuropeptide science is becoming real clinical medicine.
Questions still open
- Can kisspeptin replace hCG as the standard ovulation trigger in IVF, and would it meaningfully reduce ovarian hyperstimulation syndrome?
- Will NKB antagonists prove effective long-term for endometriosis and fibroids, or will they primarily serve as symptom management?
- What role does dynorphin — the third KNDy peptide — play therapeutically, and could targeting it add clinical value?
Common questions
What is kisspeptin and why does it matter for fertility?
How are neurokinin B blockers being used for menopause?
Read the original research
Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health.
Journal of neuroendocrinology, 34(10), e13201
Citation
Mills, Edouard G; Dhillo, Waljit S. (2022). Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health.. Journal of neuroendocrinology, 34(10), e13201. https://doi.org/10.1111/jne.13201