What is the difference between HMG and recombinant FSH?

HMG (e.g., Menopur) is a urinary-derived preparation containing both FSH and LH bioactivity (~1:1 ratio); the LH activity in highly purified HP-hMG is primarily from co-purified hCG. Recombinant FSH preparations (e.g., Gonal-F, Follistim) contain only FSH with no LH/hCG component. In women with adequate endogenous LH, recombinant FSH alone is generally sufficient for ART; HMG may offer advantages in poor responders or older patients who may benefit from additional LH activity. In men with hypogonadotropic hypogonadism, HMG's dual action closely mirrors what both FSH and LH need to do.

Is HMG approved and legal?

Yes — HMG (Menopur, Repronex) is FDA-approved for ovarian stimulation in ART and for male hypogonadotropic hypogonadism. It is a prescription pharmaceutical, not an over-the-counter compound. For male athletes, the LH and CG components make HMG prohibited under WADA S2 at all times. Research-grade or compounded HMG sold without a prescription is unregulated.

What is HMG's half-life?

The two components have different half-lives. FSH persists approximately 39–45 hours after subcutaneous injection. The LH bioactivity (delivered by hCG in HP-hMG) clears faster, with a half-life of approximately 12–15 hours IV. This means FSH activity accumulates with repeated dosing more than LH activity does, which is why Menopur is typically dosed once daily during ART stimulation.

How long does spermatogenesis induction take in men with hypogonadotropic hypogonadism?

Typically 12–24 months of combined HCG + HMG (or recombinant FSH) therapy. HCG is started first to establish intratesticular testosterone; HMG/FSH is added after 3–6 months if sperm counts remain very low. Approximately 80% of men achieve some spermatogenesis; spontaneous pregnancy rates approach 50% over the treatment course.

Hormonal

HMG

Also known as: Human Menopausal Gonadotropin, Menotropin, Menopur, Repronex, hMG, HP-hMG

A urinary-derived gonadotropin preparation containing approximately equal FSH and LH bioactivity, FDA-approved for ovarian stimulation in ART and male hypogonadotropic...

Last updated July 16, 2026

Reconstitute this peptide Buy HMG

Overview

Human menopausal gonadotropin (HMG), also called menotropin, is a purified preparation extracted from the urine of postmenopausal women. It contains approximately equal amounts of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) bioactivity, standardized at 75 IU FSH : 75 IU LH per vial. In highly purified preparations such as Menopur (HP-hMG), the LH bioactivity is provided primarily by co-purified human chorionic gonadotropin (approximately 10 IU hCG per 75 IU FSH) rather than true LH, because hCG is naturally present in postmenopausal urine. The initial U.S. approval dates to 1975; Menopur (Ferring Pharmaceuticals) received NDA approval in 2004 for ART. HMG is primarily used in reproductive medicine. In women, it induces multifollicular development for oocyte retrieval in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. In men with hypogonadotropic hypogonadism — where the pituitary fails to release adequate FSH and LH — HMG combined with HCG restores spermatogenesis by supplying both hormonal signals to the testes. FSH acts on Sertoli cells to support sperm production; HCG (substituting for LH) acts on Leydig cells to maintain intratesticular testosterone, which synergizes with FSH. HMG is a regulated pharmaceutical available only by prescription in most jurisdictions. Research-grade or compounded menotropin marketed online is unregulated and poses quality and sterility risks. WADA prohibits LH and chorionic gonadotropin in male athletes at all times under S2, which encompasses HMG. This entry is for research and educational reference only.

How it works

HMG delivers two complementary gonadotropin signals via two distinct receptor pathways. The FSH component binds FSH receptors (FSHR) — Gs protein-coupled receptors — expressed on granulosa cells of ovarian follicles and on Sertoli cells of the seminiferous tubules. In women, FSH-FSHR signaling stimulates follicular growth, aromatase expression, estrogen synthesis, and LH receptor upregulation. In men, FSH acts exclusively on Sertoli cells, which are the structural and nutritive support cells for developing sperm; Sertoli cell number (set largely during puberty by FSH) determines the quantitative ceiling for sperm production. The LH/HCG bioactivity in HMG binds the LH/CG receptor (LHCGR) on theca cells (women) and Leydig cells (men), stimulating androgen and testosterone biosynthesis via the cAMP-PKA-StAR-CYP11A1 steroidogenesis cascade. In the ovary, theca-derived androgens are aromatized by granulosa cells to estrogens; luteinization of the dominant follicle and corpus luteum progesterone production also depend on LH/HCG signaling. Because both FSH and LH are required for full reproductive function, combined HMG is clinically preferable to FSH alone in certain indications (e.g., male HH), where restoring spermatogenesis requires both Sertoli and Leydig cell stimulation.

Researched effects

Clinical Induces multifollicular development for oocyte retrieval in IVF/ART cycles
Clinical Restores spermatogenesis in men with hypogonadotropic hypogonadism when combined with HCG
Clinical Increases sperm count and pregnancy rates in men with idiopathic oligospermia (FSH supplementation)
Clinical Improves oocyte quality and competence compared to recombinant FSH alone in some ART protocols
Anecdotal Used off-label to improve sperm parameters in research/fitness contexts

Evidence levels: Clinical (human trials) · Preclinical (animal/lab) · Anecdotal (community-reported).

Dosing reference

For research reference only — not a recommendation.

Clinical / studied dosing

HMG is dosed in International Units (IU). For controlled ovarian stimulation in ART (Menopur label): starting dose 225 IU/day subcutaneously from cycle day 2 or 3; dose adjustments up to 150 IU per increment made no more than every 2 days after the initial 5 days; maximum dose 450 IU/day; treatment not to exceed 20 days. Followed by an HCG trigger (5,000–10,000 IU) or GnRH agonist trigger for final oocyte maturation. For male hypogonadotropic hypogonadism: HMG 75–150 IU intramuscularly or subcutaneously two to three times per week, combined with HCG 1,000–5,000 IU two to three times per week, adjusted to maintain serum testosterone in normal range; treatment duration commonly 12–24 months to achieve spermatogenesis. These are FDA-labeled or well-documented clinical protocols, not recommendations.

Community-reported dosing (anecdotal)

Anecdotal and research-reference only; not medical advice. HMG is not commonly used outside clinical fertility medicine in a "research" or fitness context. The small community of users discussing it typically mirror male HH protocols: HMG 75 IU subcutaneously two to three times per week alongside HCG, either during a cycle of suppressive compounds or as part of a fertility protocol. Some discuss FSH/HMG alone to improve sperm parameters in idiopathic oligospermia. All such use is off-label, requires prescription pharmaceutical product (not research-grade HMG), and should only be pursued under physician supervision. These figures are for research reference only, not instructions.

Half-life: HMG contains two components with substantially different pharmacokinetics. FSH: terminal half-life approximately 39–45 hours after subcutaneous injection (from a PK study of liquid vs. powder HP-hMG in pituitary-suppressed women); Tmax approximately 16–19 hours. LH/HCG bioactivity (primarily hCG in HP-hMG): terminal half-life approximately 12–15 hours IV, estimated ~21 hours subcutaneously; Tmax approximately 24 hours. The FSH component persists considerably longer than the LH/HCG component after each injection. Bioavailability (subcutaneous vs. intramuscular) is equivalent at approximately 74%.
Routes: subcutaneous, intramuscular

Safety & side effects

HMG carries real clinical risks, particularly in women undergoing ART. OHSS (ovarian hyperstimulation syndrome) is the primary serious adverse event: any-grade OHSS occurred in 7.2% of women in Menopur IVF clinical trials (FDA label); severe OHSS in approximately 0.6% of HMG/GnRH agonist cycles in a large retrospective series. Severe OHSS involves massive ascites, pleural effusion, hemoconcentration, and thromboembolic risk. Risk factors include PCOS, young age, high antral follicle count, and rising estradiol. The HCG trigger precipitates OHSS, and replacing it with a GnRH agonist trigger is the primary risk-reduction strategy in high-responders. Multiple gestation is another clinical risk: 35.3% of Menopur IVF pregnancies in trials were multiple gestations, carrying elevated perinatal morbidity. Injection site reactions are common with subcutaneous administration; Menopur SC causes significantly fewer local reactions than Repronex SC/IM. Immunogenicity (anti-FSH or anti-hCG antibodies) is a theoretical risk with repeated urinary-derived preparations. WADA prohibits luteinizing hormone (LH) and chorionic gonadotropin (CG) and their releasing factors in male athletes at all times under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics); because HMG delivers both LH bioactivity (via hCG) and FSH, it falls within the S2 prohibition for male competitors. This information is for research and educational reference only.

Research summary

HMG has one of the longest clinical evidence histories in reproductive medicine, with use in fertility treatment since the 1960s and FDA approval since 1975. Evidence for its two primary indications is robust. In ART/IVF, multiple large RCTs and meta-analyses have compared HMG to recombinant FSH preparations; results are broadly similar for live birth rates, with some evidence that the LH activity in HP-hMG may improve oocyte competence and blastocyst quality in some patient populations, though this remains debated. In male hypogonadotropic hypogonadism, HCG+HMG (or HCG+recombinant FSH) is the standard spermatogenesis induction protocol; RCTs confirm spermatogenesis in most treated men over 12–24 months, with pregnancy rates around 50%. For idiopathic male infertility and oligospermia, FSH/HMG shows a modest evidence base of meta-analyzed RCTs reporting improved sperm parameters and pregnancy rates, though effect sizes vary. The evidence for any off-label fitness or performance-enhancement use is anecdotal and the compounds' pharmacological effects (FSH on Sertoli cells, LH on Leydig cells) do not map onto performance in any direct or well-studied way. OHSS risk management is the primary ongoing clinical research area, with growing adoption of GnRH agonist triggers to reduce HCG-driven OHSS in high-risk patients.

FAQ

What is the difference between HMG and recombinant FSH?: HMG (e.g., Menopur) is a urinary-derived preparation containing both FSH and LH bioactivity (~1:1 ratio); the LH activity in highly purified HP-hMG is primarily from co-purified hCG. Recombinant FSH preparations (e.g., Gonal-F, Follistim) contain only FSH with no LH/hCG component. In women with adequate endogenous LH, recombinant FSH alone is generally sufficient for ART; HMG may offer advantages in poor responders or older patients who may benefit from additional LH activity. In men with hypogonadotropic hypogonadism, HMG's dual action closely mirrors what both FSH and LH need to do.
Is HMG approved and legal?: Yes — HMG (Menopur, Repronex) is FDA-approved for ovarian stimulation in ART and for male hypogonadotropic hypogonadism. It is a prescription pharmaceutical, not an over-the-counter compound. For male athletes, the LH and CG components make HMG prohibited under WADA S2 at all times. Research-grade or compounded HMG sold without a prescription is unregulated.
What is HMG's half-life?: The two components have different half-lives. FSH persists approximately 39–45 hours after subcutaneous injection. The LH bioactivity (delivered by hCG in HP-hMG) clears faster, with a half-life of approximately 12–15 hours IV. This means FSH activity accumulates with repeated dosing more than LH activity does, which is why Menopur is typically dosed once daily during ART stimulation.
What is OHSS and how serious is it?: Ovarian hyperstimulation syndrome (OHSS) is the main serious risk of HMG in women. Severe OHSS (affecting approximately 0.6% of stimulation cycles in older data, up to ~1–2% in some series) involves massive fluid shifts, ascites, pleural effusion, hemoconcentration, and thromboembolic risk. It is triggered primarily by the HCG ovulation trigger. In high-risk patients, switching to a GnRH agonist trigger dramatically reduces OHSS risk. OHSS is managed supportively; severe cases may require hospitalization.
How long does spermatogenesis induction take in men with hypogonadotropic hypogonadism?: Typically 12–24 months of combined HCG + HMG (or recombinant FSH) therapy. HCG is started first to establish intratesticular testosterone; HMG/FSH is added after 3–6 months if sperm counts remain very low. Approximately 80% of men achieve some spermatogenesis; spontaneous pregnancy rates approach 50% over the treatment course.

References

All content is for research and educational use only and is not medical advice. Products are sold for laboratory research only and are not for human consumption.