Peptide Therapy Foundations: Hormonal & Sexual Health
Course Details
This course examines the peptides that act on sexual function and the hormonal axis that governs reproduction. It is written for clinicians who want to understand how these agents influence desire, arousal, and the upstream signaling of the reproductive system, and how the evidence behind each one should be read.
The lessons cover two mechanistic approaches. PT-141, a melanocortin receptor agonist, acts centrally on pathways tied to sexual desire and arousal. Kisspeptin-54 and Kisspeptin-10 sit further upstream, signaling through the KISS1 receptor to drive gonadotropin-releasing hormone and the hypothalamic-pituitary-gonadal axis. The two kisspeptin isoforms differ in size and signaling behavior, and the lessons keep them distinct.
Each lesson follows the same clinical lens: what the agent is, how it works, what the evidence shows, and what a practitioner weighs before applying it. Together they map the hormonal and sexual-health peptides as a group so you can reason about each one against the others.
SSRP FACULTY
William Seeds, MD
William Seeds, MD
William Seeds, MD
Before establishing the SSRP Institute, Dr. Seeds served as a board-certified orthopedic surgeon and sports medicine specialist for nearly three decades, including Chief of Surgery, Orthopedic Residency Site Director, and Director of The Ohio Bone & Joint Institute for University Hospitals.
His significant contributions to sports medicine have been recognized at the NFL Hall of Fame. He has consulted for athletes across all major sports leagues, including the NFL, NHL, MLB, NBA, and even the performers on “Dancing with the Stars.”
Through his research at the SSRP Institute, Dr. Seeds continues to explore the cellular pathways and mechanisms that positively impact disease and dysfunction in the body as well as optimize physical performance.
Kisspeptin-10
In-ProgressLesson Resources
Overview
Kisspeptin-10, also known as metastin, is the smallest bioactive fragment of Kisspeptin-54. This 10 amino acid sequence is an agonist at the KISS1 receptor, a GPR54 class A GPCR coupled through G alpha q11. Its binding affinity is comparable to that of the parent Kisspeptin-54, yet its half life is short, on the order of four minutes after intravenous dosing. As of 2024 it appears on the WADA prohibited list, and it remains investigational with no FDA approval.
This lesson covers the receptor signaling, the regulation it exerts over reproductive hormones, the pleiotropic effects reported beyond reproduction, and the dosing and safety signals seen in early human and animal work.
Mechanism and HPG axis regulation
KISS1 receptor activation drives phospholipase C beta, generating IP3 and DAG, intracellular calcium mobilization, and PKC activation. Downstream ERK1/2 and p38 MAPK signaling promotes gonadotropin releasing hormone gene expression and neuronal firing. Beta arrestin 2 supports ERK activity while beta arrestin 1 inhibits it.
Acting as an upstream gatekeeper, Kisspeptin-10 binds KISS1 receptors on GnRH neurons in the arcuate nucleus and preoptic area. This stimulates GnRH release into portal circulation, which drives pituitary LH and FSH secretion and, in turn, gonadal steroidogenesis. A GnRH antagonist negates these upstream effects, confirming the pathway.
The KNDy neuron model
The KNDy neuron model frames three co-expressed peptides in the arcuate nucleus: kisspeptin, neurokinin B, and dynorphin. Neurokinin B drives the stimulatory pulse, dynorphin provides inhibitory control, and kisspeptin causes the GnRH release. Together they generate the pulsatile rhythm. Where pulsatility is lost, Kisspeptin-10 can restore it.
Population-dependent response and pleiotropic effects
In human trials, IV boluses raised LH within 30 minutes, and sustained infusion increased LH and pulse frequency. Very high bolus doses produced a paradoxical blunting consistent with receptor desensitization. Response varies by population: robust in men, blunted in the early follicular phase, enhanced preovulatory and postmenopausal, and notably responsive in hypothalamic amenorrhea where the hypothalamic block is bypassed.
Reported pleiotropic actions include anti-metastatic effects tied to KISS1 as a metastasis suppressor gene, bone protection via the SRC and DUSP18 axis suppressing osteoclast formation, and metabolic effects on glucose handling, GIP, and GLP-1.
Key clinical points
- Kisspeptin-10 acts upstream of GnRH, preserving endogenous HPG axis feedback rather than overriding it.
- Its short half life points toward pulsatile or frequent dosing; reported empirical subcutaneous practice is 100 to 200 micrograms daily.
- Response is dimorphic in females and tied to menstrual phase; monitor LH, FSH, testosterone, and estradiol against baseline.
- Limited blood brain barrier penetration relative to Kisspeptin-54 is an open question for subcutaneous clinical use.
- It is WADA prohibited and FDA restricted; cautions include tachyphylaxis, possible vasoconstriction at higher doses, and hormone-sensitive cancers.
Questions? Our Provider Care Team is here to help.
We'd love to help you determine the best next steps on your Cellular Medicine journey.
Continue your learning journey
VIEW ALLAging-Associated Decline of Phosphatidylcholine Synthesis is a Malleable Trigger of Natural Mitochondrial Aging
Dr. Seeds explores how age-related decline in phosphatidylcholine synthesis may contribute to mitochondrial aging and why that matters in Cellular Medicine. This discussion connects membrane integrity, mitochondrial function, methylation, and metabolic resilience, while highlighting how this pathway may be more modifiable than we once thought.
1. Managing shingles outbreaks in GLP-1 patient through peptides (0:40)
2. Peptide strategies in suspected ALS (15:56)
3. Improving durability in dementia treatment (25:08)
In this bonus episode from the MM15 Virtual Summit, Dr. Seeds addresses an important question around the use of GLP-1s for metabolic balancing in patients who do not need to lose weight. He shares his perspective on what may be considered microdosing, along with the clinical thought process he uses when determining appropriate dosing in these more nuanced cases.
Additional questions from the MM15 Virtual Summit can be found in our accompanying article here: [insert article link]
Access the full MM15 Course here: Mastermind 15 on Aesthetics
The Limits of Alternative Peptide Delivery
Dr. Seeds reviews oral, sublingual, and transdermal peptide delivery, and explains why subcutaneous injection remains the gold standard for most peptides. (Question Link)
A Deeper Look at the RAAS System
Dr. Seeds uses this Rabbit Holes episode to build on Journal Club Episode 87, revisiting the renin-angiotensin-aldosterone system and its broader role in cellular signaling. The discussion focuses on receptor balance, local tissue effects, and the mechanisms linking RAS disruption to inflammation, fibrosis, and mitochondrial stress.(Article Link)
The Renin–Angiotensin–Aldosterone System (RAAS): Beyond Cardiovascular Regulation
Dr. Seeds unpacks how RAS receptor balance drives inflammation, fibrosis, mitochondrial dysfunction, and tissue remodeling, far beyond its classical role in blood pressure regulation. (Article Link)
1. SSRI tapering resistance, anxiety during weaning (0:40)
2. Progressive multifocal dystonia (13:27)
3. Complex type 2 diabetes case in a lean, athletic patient (28:32)