HMG (Human Menopausal Gonadotropin)

HMG (Human Menopausal Gonadotropin)

HMG is an injectable fertility hormone that does what hCG can't: it restarts sperm production. Your testicles run on two separate signals from the brain, one for making testosterone (LH) and one for making sperm (FSH).
hCG (Human Chorionic Gonadotropin)
hCG (Human Chorionic Gonadotropin) covers the testosterone signal. HMG covers both. That's the whole reason it exists as a separate product.
HMG is mostly used when hCG alone isn't enough to restart sperm production, either because they've been on TRT or a steroid cycle for a long time, or because their underlying issue is more pituitary-wide than just an LH problem. In women, it's used clinically for ovulation induction and IVF stimulation, particularly when both FSH and LH activity are needed (as in hypothalamic amenorrhoea) or when clomiphene and letrozole haven't worked.

Deep-dive

HMG is extracted and purified from the urine of postmenopausal women, whose pituitaries are pumping out high levels of FSH and LH because their ovaries no longer respond. Modern highly-purified preparations (Menopur is the most common, followed by Menogon, Repronex, and others) are standardised so that each 75 IU vial contains 75 IU of FSH bioactivity and 75 IU of LH bioactivity. Worth knowing: most of the LH-like activity in HP-hMG actually comes from hCG, not LH itself, with roughly 10 IU of hCG per 75 IU of urinary FSH. This is because hCG binds the same receptor as LH but lasts much longer, so a small amount of hCG produces the same bioactivity as a larger amount of LH. Practically, this means HMG is essentially "FSH plus a small dose of hCG" rather than a true LH product.
Why FSH matters for men. The standard fertility protocol for men starts with hCG alone, because hCG is cheaper, more available, and sufficient on its own in many cases. But hCG only drives intratesticular testosterone via Leydig cells. Sperm production requires Sertoli cell stimulation, and Sertoli cells respond to FSH. In men with secondary hypogonadism, hCG alone induces sperm in the ejaculate in many cases, but the counts are often suboptimal. The pattern is consistent in the literature: once spermatogenesis is initiated with hCG plus HMG and HMG is dropped, sperm counts decline gradually, confirming that FSH is essential for quantitatively normal sperm production. A retrospective study of 112 men with congenital hypogonadotropic hypogonadism found that adding HMG or recombinant FSH to hCG produced sperm in the ejaculate in 85.7% of patients, with comparable outcomes between HMG and rFSH. There's also a case report of a man with isolated FSH deficiency (normal LH and testosterone, very low FSH, azoospermic) who recovered spermatogenesis on HMG alone.
The hCG-first, HMG-second algorithm. In secondary hypogonadism or post-TRT/post-cycle recovery, the standard sequence is hCG first (typically 1,500-3,000 IU 2-3 times weekly), and if sperm haven't appeared in the ejaculate after 4-6 months, add HMG or recombinant FSH at 75-150 IU 2-3 times weekly. This is because spermatogenesis from a fully shut-down state takes time (the full cycle from spermatogonia to mature sperm is about 74 days, and the testes have to re-establish the supporting tissue first). Adding FSH from day one is sometimes done in men with very small testes (under 4 mL), prior pre-pubertal hypogonadism, or a long history of AAS use, where Sertoli cell function is suspected to be more impaired. For everyone else, hCG monotherapy first, HMG added only if needed, keeps cost and injection burden lower.
Post-cycle and post-TRT recovery. In the broader recovery context, HMG sits in the toolkit alongside hCG, SERMs (clomiphene, tamoxifen, enclomiphene), and aromatase inhibitors. The clinical algorithm is roughly: stop the suppressive compound, start hCG to wake up the Leydig cells, add a SERM to push the pituitary back into producing its own LH and FSH, and add HMG if FSH levels stay suppressed and sperm don't return. In a series of azoospermic men with hypogonadism after TRT, combinations of hCG with FSH (HMG or rFSH), clomiphene, tamoxifen, or anastrozole produced a mean recovery to 22 million sperm/mL in around 4 months. For men recovering from years of heavy AAS use, particularly multi-compound or 19-nor cycles (nandrolone, trenbolone), HMG is more often necessary than for men coming off a single short course of testosterone.
Women. HMG is one of the workhorse drugs in reproductive endocrinology. The two main use cases:
  • Ovulation induction in women who aren't ovulating. First-line for unexplained anovulation is letrozole or clomiphene. If those fail, HMG (or pure FSH) is the next step. In women with hypothalamic or hypopituitary amenorrhoea, where both LH and FSH are deficient (often from low body fat, overtraining, prolonged stress, or pituitary issues), HMG is preferred over pure FSH because the LH activity is genuinely needed for normal follicle development and oestrogen production. In women with PCOS, where LH is already elevated, pure FSH or a low-LH preparation is usually preferred to avoid pushing LH higher. A 2025 trial of 174 women with PCOS used letrozole 2.5 mg combined with sequential HMG and produced an 85% ovulation rate and 33% ongoing pregnancy rate, with the lower letrozole dose actually outperforming the higher dose on endometrial quality and mono-follicular development.
  • Controlled ovarian stimulation for IVF. HMG is used to grow multiple follicles before egg retrieval. The big question in the literature has been whether HMG or pure recombinant FSH produces better outcomes. A meta-analysis of seven trials with 2,159 women found HMG was associated with a roughly 18% higher live birth rate than recombinant FSH (relative risk 1.18, absolute difference 4%) in long down-regulation protocols. A separate meta-analysis focused on highly-purified HMG vs rFSH found a clear advantage for HP-HMG in IVF cycles (odds ratio 1.31 for ongoing pregnancy/live birth) but no difference in ICSI cycles. The proposed reason is that the LH/hCG component of HMG supports better steroid environment in the follicle and possibly better oocyte quality, but the difference is modest and other meta-analyses have found roughly equivalent outcomes between the two. Most clinics choose based on patient profile rather than blanket preference.
OHSS in women. The big risk specific to women is ovarian hyperstimulation syndrome, where the ovaries overrespond to gonadotropin stimulation and leak fluid into the abdomen and lungs. Mild forms occur in up to a third of IVF cycles; moderate to severe forms in 3-8%. Risk factors are young age, low BMI, PCOS, high follicle counts, and high AMH. The trigger for severe OHSS is the hCG given for ovulation, not HMG itself, but HMG is what grows the excessive follicle pool that makes OHSS possible. This is why protocols in high-risk women either avoid hCG triggers (using a GnRH agonist trigger instead) or freeze all embryos and transfer in a later cycle.
HMG vs recombinant FSH vs hCG: when each makes sense. Recombinant FSH (Gonal-F, Puregon) is pure FSH with no LH activity, made in cell culture. HMG has FSH and LH (mostly via hCG) activity in a 1:1 ratio. hCG has only LH-like activity. For men, the LH role is filled by hCG (which is cheaper and easier to dose), so HMG and recombinant FSH are roughly interchangeable as the FSH source. Recombinant FSH is purer, more consistent batch-to-batch, and easier to administer in pre-filled pens, but more expensive. HMG is cheaper per IU, has the LH/hCG activity built in (occasionally useful in men where the hCG dose has been minimised), and is the traditional choice. For women, the choice depends on whether LH activity is wanted or not, as outlined above.
Older men and limitations. HMG only works if there's a functional testicle to stimulate. In primary testicular failure (high baseline FSH and LH, small testes that have been damaged by chemo, radiation, mumps, Klinefelter, or simply age), no amount of HMG will restart sperm production. The same applies to women with premature ovarian insufficiency or significantly diminished ovarian reserve, the eggs aren't there. Long-term safety data on repeated cycles is reasonable for fertility use (decades of clinical experience), but HMG is not used as a long-term wellness or anti-ageing tool, so there's no data on chronic multi-year use in healthy populations.

Dosage:

  • Men, adjunct to hCG for sperm production (secondary hypogonadism, post-TRT, post-AAS): 75-150 IU subcutaneous, 2-3 times per week, added to existing hCG (typically 1,500-3,000 IU 2-3x weekly). Most protocols start with hCG alone, then add HMG if sperm haven't appeared after 4-6 months. Higher end (150 IU 3x weekly) for men with very small baseline testicular volume, prolonged heavy AAS history, or pre-pubertal hypogonadism
  • Men, full induction in congenital hypogonadotropic hypogonadism: hCG 1,500-2,000 IU 2-3x weekly plus HMG 75-150 IU 2-3x weekly. Continue for at least 6-12 months. Expect testicular volume increase first (over 3-6 months), sperm in the ejaculate second (often 6-12 months in)
  • Women, ovulation induction (hypothalamic or hypopituitary amenorrhoea, clomiphene/letrozole failure): typically starting at 37.5-75 IU subcutaneous daily, titrated by ultrasound and oestradiol monitoring. This is clinic-managed, not a self-administered protocol
  • Women, PCOS ovulation induction: lower starting doses (37.5 IU daily) due to higher OHSS risk, often combined with letrozole 2.5 mg on cycle days 3-7 followed by HMG. Clinic-managed
  • Women, IVF stimulation: 150-300 IU daily as part of a long, short, or antagonist protocol. Dose adjusted by response. Clinic-managed
  • Injection method: subcutaneous in the belly fat or thigh is standard. Some older preparations are intramuscular only, but most modern HP-HMG (Menopur, Menogon) is approved subcutaneous and is much less painful that way. Reconstituted with bacteriostatic water and used within the timeframe on the label (typically 28 days refrigerated)
  • Practical note for men: because HMG contains a small amount of hCG already, you can sometimes reduce your separate hCG dose slightly when adding HMG. Don't do this without bloodwork, the hCG content varies by preparation and isn't enough to replace a meaningful hCG dose on its own

Here's what you can expect:

If you're a man adding HMG to hCG for fertility, the timeline is slow. Testicular volume typically increases over 3-6 months. Sperm in the ejaculate often takes 6-12 months from a fully shut-down baseline, occasionally longer if you've been on TRT or AAS for many years. Don't expect anything in the first 8-12 weeks beyond gradual testicular volume increase. Subjective effects on libido, mood, or energy are minimal beyond what hCG itself produces, HMG's job is the FSH signal, which is felt at the testicular level, not systemically.
If you're a woman on HMG for ovulation induction, you'll feel essentially nothing for the first several days. Then, as follicles grow, you may notice mild bloating, breast tenderness, or pelvic fullness. Your clinic will monitor with ultrasound and oestradiol every 2-4 days and trigger ovulation with an hCG injection when a dominant follicle reaches 17-18 mm. The whole cycle is roughly 10-14 days from start to trigger.
If you're on HMG for IVF stimulation, expect more pronounced bloating, breast tenderness, mood swings, and pelvic pressure as multiple follicles develop. This is normal and resolves after egg retrieval. The intense fluid shift and discomfort of OHSS, if it happens, is in a different category and needs immediate attention.
What HMG won't do: it won't raise testosterone or estradiol on its own in someone with normal pituitary function and intact gonads, the negative feedback will adjust your endogenous output. It only meaningfully shifts the system when endogenous gonadotropin is low or absent.

Side effects & risks:

  • Injection site reactions. Mild redness, soreness, or bruising at the injection site. Subcutaneous HMG is generally well-tolerated, less painful than intramuscular versions
  • Headaches, bloating, fatigue, mood changes. Common at therapeutic doses in both sexes, usually mild and resolve when treatment stops
  • Ovarian hyperstimulation syndrome (women). The serious risk specific to women. Symptoms: severe abdominal pain, bloating, rapid weight gain, nausea, vomiting, shortness of breath. Mild OHSS is common and self-limiting; moderate to severe requires medical attention and occasionally hospitalisation. Higher risk in women under 35, low BMI, PCOS, high AMH, high follicle count. Mostly a concern in IVF cycles where multiple follicles are deliberately stimulated, not ovulation induction protocols aiming for a single follicle
  • Multiple pregnancy. Real risk in women, because HMG can recruit more than one follicle. Twin and triplet pregnancy rates are higher than baseline. Modern protocols try to mitigate this with careful monitoring and conservative dosing in ovulation induction, and with single embryo transfer in IVF
  • Gynecomastia and oestradiol elevation (men). Possible because the FSH stimulation supports Sertoli cell aromatase activity, and the LH-like component drives testosterone that can convert to oestradiol. Less of a concern than with high-dose hCG monotherapy, but worth tracking if you're already estradiol-prone
  • Ovarian torsion (women). Rare but documented, enlarged ovaries during stimulation can twist on their pedicle. Sudden severe one-sided pelvic pain needs immediate evaluation
  • Thromboembolism (women). Mainly in the setting of severe OHSS, where haemoconcentration and inflammatory mediators raise clotting risk. Rare at standard ovulation induction doses
  • Antibody formation. Urinary-derived HMG is theoretically immunogenic given it contains other urinary proteins beyond FSH and LH. Clinically meaningful anti-FSH antibodies are very rare, but allergic reactions at injection sites occur in a small percentage
  • Underlying contraindications: primary ovarian failure, primary testicular failure (it won't work), uncontrolled thyroid or adrenal dysfunction, pituitary or hypothalamic tumours unless treated, undiagnosed vaginal bleeding, ovarian cysts or enlargement not from PCOS, pregnancy, hormone-sensitive tumours of the reproductive tract
  • Quality and sourcing. Pharmaceutical HMG (Menopur, Menogon, Repronex, IVF-M) is well-characterised and reliably potent. Research-grade or underground HMG varies wildly. The hormones in HMG are protein-based and degrade easily with heat, light, and time, sourcing matters more here than for small-molecule drugs
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Blood markers

FSH, LH, total and free testosterone, oestradiol (sensitive assay), SHBG, baseline before starting. In men, these establish whether you have primary or secondary hypogonadism (HMG only works on a functional testicle responding to absent or low gonadotropin). In women, they help characterise the underlying cause of anovulation.
AMH and antral follicle count (women), baseline. Critical for predicting ovarian response and OHSS risk. High AMH (above 3.5 ng/mL) flags higher OHSS risk; very low AMH suggests poor response regardless of dose.
Semen analysis (men), baseline and every 3 months while on therapy. This is the only reliable way to know if HMG is doing its job. Don't rely on serum FSH or testosterone alone, sperm count and motility are the real endpoint.
Oestradiol (sensitive assay) during stimulation (women). Tracked every 2-4 days during ovulation induction and IVF to gauge response and avoid OHSS. This is clinic-managed.
Prolactin, TSH, baseline. Hyperprolactinaemia and untreated thyroid dysfunction both interfere with the HPG axis and need to be addressed before gonadotropin therapy will work properly.
Pregnancy test (women), routinely before starting each cycle. HMG isn't safe in pregnancy and stimulation in an undetected early pregnancy compounds OHSS risk.
Who actually needs full bloodwork: anyone on HMG, men and women alike. Unlike a daily wellness compound, HMG is always used in a clinical context with a specific endpoint (sperm count or pregnancy), and the labs above are what guide dosing and stopping. If you're a man on HMG as a TRT-adjunct or post-cycle adjunct, semen analysis at baseline and at 3-6 month intervals is the most important single test.
HMG is a prescription medication in essentially all jurisdictions. Use under appropriate clinical guidance.