HMG (Human Menopausal Gonadotropin)

Mechanism

HMG is a fertility medication that combines the two key reproductive hormones — FSH and LH — in a 1:1 ratio. FSH stimulates egg follicle growth in women and sperm production in men, while LH triggers ovulation in women and testosterone production in men. It is extracted from the urine of postmenopausal women (who produce high levels of these hormones). In the peptide community, it is sometimes used by men on TRT or post-cycle therapy to maintain or restore both testosterone production and sperm count simultaneously.

Effects

REPRODUCTIVE (FEMALE): Primary FDA-approved indication. Combines FSH + LH in 1:1 ratio — provides both key reproductive hormones. FSH stimulates ovarian follicle growth and maturation (granulosa cell proliferation, aromatase induction). LH supports theca cell androgen production (substrate for estrogen synthesis) and is required for final follicular maturation. Used in IVF/IUI protocols to stimulate multiple follicle development. Significantly increases chances of successful ovulation and fertilization in women with PCOS, unexplained infertility, or hypogonadotropic hypogonadism. REPRODUCTIVE (MALE): Increasingly used in peptide community. FSH acts on Sertoli cells to support spermatogenesis — stimulates androgen-binding protein (ABP) and inhibin B production. LH acts on Leydig cells for intratesticular testosterone synthesis. The FSH component is what distinguishes HMG from HCG — HCG provides only LH-like activity. For men who need both testosterone support AND fertility preservation, HMG addresses BOTH Leydig cell (testosterone) AND Sertoli cell (sperm) function. Particularly valuable for severe oligospermia during or after TRT. ENDOCRINE: Direct gonadotropin replacement — FSH and LH are the master hormones controlling the reproductive axis. In men: increases both intratesticular testosterone AND sperm production. In women: drives folliculogenesis and estrogen production. CARDIOVASCULAR: No direct effects. Estrogen fluctuations from ovarian stimulation can affect fluid balance. METABOLIC: No direct metabolic effects. RISK: Ovarian hyperstimulation syndrome (OHSS) in women — potentially life-threatening. Requires close monitoring with ultrasound and estradiol levels during IVF cycles. Multiple pregnancy risk. In men: risk is minimal at therapeutic doses. Tier 3: Standard of care in reproductive endocrinology. In the peptide community, increasingly used as an alternative or supplement to HCG for men who need comprehensive HPG axis support.

Practitioner Guide

DOSING TIPS: FEMALE (IVF/IUI): 75-150 IU IM or SubQ daily, starting cycle day 2-3, adjusted based on ultrasound monitoring and estradiol levels. Typical cycle: 8-12 days of stimulation. Requires physician oversight and serial monitoring. MALE (Fertility): 75-150 IU IM or SubQ 2-3x/week, often combined with HCG. For spermatogenesis induction: HCG 1500-2000 IU 2-3x/week + HMG 75-150 IU 2-3x/week for 3-6 months (sperm maturation takes ~74 days). Some practitioners start HCG alone for 3 months, then add HMG if sperm count remains low. RECONSTITUTION: Menopur comes as lyophilized powder + diluent. Reconstitute per package instructions. For compounded HMG: standard BAC water reconstitution. Multiple vials can be reconstituted with the same diluent (piggyback technique) to reduce injection volume. INJECTION SITE: Subcutaneous (abdominal) for most protocols. IM (gluteal) for larger doses. SubQ is standard for modern IVF protocols. TIMING: Evening injection for IVF protocols (standard). For male fertility: no specific timing, but consistency matters. SUPPLEMENT SYNERGIES: FEMALE: Folate/methylfolate (800-1000mcg/day) — essential for egg quality. CoQ10 (600mg/day) — improves oocyte mitochondrial function. DHEA (25-75mg/day) — for diminished ovarian reserve (under physician guidance). Vitamin D (2000-5000 IU/day). MALE: HCG (primary LH support) + HMG (adds FSH for Sertoli cells). Zinc (50mg/day) + Selenium (200mcg/day) — support spermatogenesis. L-carnitine (2g/day) — improves sperm motility. Folate + B12 — support DNA methylation in spermatogenesis. CYCLING: FEMALE: Per IVF cycle protocol (typically one stimulation per cycle). MALE: Continuous 3-6 months for spermatogenesis induction, then reassess with semen analysis. STACKING: Male fertility: HCG + HMG + Clomid (or Enclomiphene). TRT + Fertility: Testosterone + HCG (testicular support) + HMG (spermatogenesis). CONTRAINDICATION NUANCES: FEMALE: Primary ovarian insufficiency — will not respond. Unexplained gynecological bleeding. Sex hormone-dependent tumors. Pregnancy. MALE: Testicular failure (primary hypogonadism) — elevated FSH indicates testes cannot respond. Prostate cancer (androgen-dependent). STORAGE: Lyophilized — room temperature (Menopur) or refrigerated. Reconstituted — use within 28 days, refrigerate. PATIENT EDUCATION: HMG provides both FSH and LH — the two hormones your brain normally sends to your reproductive organs. For men on TRT worried about fertility: HCG tells your testes to make testosterone, but HMG goes further by also supporting sperm production through FSH. Think of HCG as 'half the signal' and HMG as 'the complete signal.' Spermatogenesis takes 3 months — be patient. Regular semen analysis is essential for monitoring.

Evidence

• Comparative Effectiveness of Recombinant Human Follicle-Stimulating Hormone:Recombinant Human Luteinizing Hormone in a 2:1 Ratio versus Highly Purified Human Menopausal Gonadotropin Alone in Ovarian Stimulation for Medically Assisted Reproduction Treatment Using in vitro Fertilization/Intracytoplasmic Sperm Injection: A Systematic Review and Meta-Analysis.

  Dahan MH, Schwarze JE, Gupta SS, Hayward B, Fischer R, Esteves SC, Chen MJ, Silverberg KM, Guzmán L, Santi D, Feferkorn I, D'Hooghe TM, Alviggi C (2026) — Gynecologic and Obstetric Investigation — PMID: 41729769

  Across six studies comprising 5,287 ovarian stimulation cycles, r-hFSH:r-hLH 2:1 yielded more oocytes and a higher clinical pregnancy rate than HP-hMG alone, while live-birth conclusions remained uncertain due to limited data. This functions as comparative evidence that hMG remains a standard reproductive stimulant but may be outperformed in some IVF settings by recombinant combinations.

  moderate

• Clinical efficacy and safety of two highly purified human menopausal gonadotropins in women undergoing in vitro fertilization.

  Rao KA, et al. (2025) — Reproduction and Fertility — PMID: 40445794

  Among 150 women undergoing controlled ovarian stimulation for IVF, Gynogen HP and Menopur produced similar oocyte retrieval counts, fertilization outcomes, pregnancy metrics, and safety results. The study supports therapeutic equivalence of two highly purified hMG preparations rather than superiority of one over the other.

  moderate

Research Summary

TIER 1 (Gold Standard): FDA-approved product labeling for Menopur, Repronex. Cochrane reviews on gonadotropins for ovulation induction. Multiple RCTs comparing HMG vs. recombinant FSH for IVF outcomes (Cochrane meta-analysis: similar efficacy, HMG may improve live birth rates in some subgroups). Van Wely et al., 2011 — HMG vs. recombinant FSH meta-analysis. ESHRE guidelines on ovarian stimulation protocols. TIER 2 (Strong): Bouloux et al., 2003 — HMG for male hypogonadotropic hypogonadism fertility induction. ASRM (American Society for Reproductive Medicine) practice guidelines. Endocrine Society guidelines on male infertility. Extensive pharmacokinetics literature for urinary gonadotropins. TIER 3 (Moderate): Male fertility preservation protocols from performance medicine practitioners. Clinical protocols combining HCG + HMG for TRT-induced infertility. International IVF clinic protocols. KEY FINDINGS: (1) HMG is a proven, FDA-approved fertility treatment with decades of clinical use. (2) For men, it addresses the FSH gap that HCG alone cannot cover. (3) Comparable efficacy to recombinant FSH in IVF. (4) OHSS risk in women requires careful monitoring. (5) For male fertility during TRT, HCG + HMG is the gold standard combination. GAPS: Optimal HMG dosing for male fertility preservation during TRT (no RCTs). Long-term safety in men with continuous use. Head-to-head with recombinant FSH for male spermatogenesis. ACTIVE TRIALS: Numerous ongoing IVF trials on ClinicalTrials.gov.