Follitropin alfa is recombinant human follicle-stimulating hormone (FSH), made in Chinese hamster ovary cells. FSH is the pituitary hormone that drives egg development in women and sperm production in men. The best-known product is EMD Serono’s Gonal-f, first approved in the EU in 1995 and in the US in 1997. A closely related recombinant FSH, follitropin beta, is sold in the US as Organon’s Follistim AQ.
Most follitropin alfa is used in women, for ovulation induction and IVF. In men, the US Gonal-f label has one indication: starting sperm production in infertile men with hypogonadotropic hypogonadism (low testosterone and absent sperm production caused by pituitary or hypothalamic failure). It is always given together with hCG, which supplies the LH-like signal that FSH lacks. FSH does not raise testosterone, and we found no study showing a muscle-building effect.
This page summarizes what the FDA and EMA labels, clinical trials and guidelines report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Gonadotropin; recombinant human FSH (glycoprotein hormone) |
| Brands / approval | Gonal-f and Gonal-f RFF Redi-ject (EMD Serono; US 1997, EU 1995); EU biosimilars Ovaleap (2013) and Bemfola (2014). Follitropin beta: Follistim AQ (Organon; US 1997) |
| Route | Subcutaneous injection |
| US strengths | Gonal-f multi-dose vials of 450 IU and 1,050 IU; Gonal-f RFF Redi-ject pens of 300, 450 and 900 IU |
| Labeled dose in men | 150 IU three times weekly with hCG, after 3–6 months of hCG alone; up to 300 IU three times weekly, for up to 18 months |
| Half-life (label) | 24 ± 11 h after one dose in women; 41 ± 14 h after one dose and 32 ± 4 h after repeated doses in healthy men |
| Key mechanism fact | Acts on Sertoli cells in the testis; testosterone comes from the separate LH signal (hCG) |
| US status | Prescription biologic; not listed among the anabolic steroids in DEA Schedule III |
| WADA status | Not named on the 2026 Prohibited List; S2.2.1 names hCG, LH, GnRH and kisspeptin as banned testosterone-stimulating peptides in males |
What it is
FSH is a glycoprotein hormone made of two protein chains. The Gonal-f label describes follitropin alfa as having an alpha subunit of 92 amino acids and a beta subunit of 111, with a structure “indistinguishable” from natural human FSH and a molecular weight of about 31 kDa (Gonal-f label).
Before recombinant products, FSH for fertility treatment came from the urine of postmenopausal women, as in hMG (menotropins), which supplies both FSH and LH activity. Recombinant FSH contains only FSH, which is why the labels require hCG alongside it in men.
| Product | Active substance | Made in | Molecular weight (label) | US indications in men |
|---|---|---|---|---|
| Gonal-f (vials) | Follitropin alfa | CHO cells | About 31 kDa | Induction of spermatogenesis in hypogonadotropic hypogonadism |
| Gonal-f RFF Redi-ject (pen) | Follitropin alfa | CHO cells | Same protein | None (women only) |
| Follistim AQ (cartridge) | Follitropin beta | CHO cells | About 40 kDa | Induction of spermatogenesis in hypogonadotropic hypogonadism |
Sources: Gonal-f label; Gonal-f RFF Redi-ject label; Follistim AQ label.
Both labels describe the same 92- and 111-amino-acid subunits, but give different molecular weights for the finished proteins.
What FSH does in men
In the testis, two hormone signals work together:
- LH stimulates the Leydig cells to make testosterone; without LH and FSH stimulation, the AUA/ASRM guideline notes, Leydig cells do not secrete testosterone and sperm production is disrupted (AUA/ASRM guideline). hCG is used as a stand-in for LH.
- FSH acts on the Sertoli cells, the “nurse” cells that support developing sperm; in men given recombinant FSH, testicular biopsies showed Sertoli-cell proliferation (Dwyer et al., JCEM 2013). The Follistim label calls FSH “the pituitary hormone responsible for spermatogenesis” (Follistim AQ label).
When the pituitary stops making both hormones, as in hypogonadotropic hypogonadism or during suppression by external androgens, both signals have to be replaced. FSH alone cannot do this, because without hCG or LH the testis makes little testosterone.
Does FSH raise testosterone? No. A 2025 meta-analysis of 41 studies found that testosterone and testis-volume increases were the same with hCG alone and with hCG plus FSH; only sperm output was higher with the combination (Muir et al., Clin Endocrinol 2025). Claims that FSH has anabolic or “testosterone-boosting” effects have no support in the trial literature.
Pharmacokinetics
The Gonal-f label reports these values after subcutaneous injection (Gonal-f label):
| Parameter (mean ± SD) | Healthy women, 150 IU once | Healthy men, 225 IU once | Healthy men, 225 IU daily × 7 |
|---|---|---|---|
| Peak level (Cmax) | 3 ± 1 IU/L | 2.5 ± 0.8 IU/L | 8.3 ± 0.9 IU/L |
| Time to peak | 16 ± 10 h | 20 ± 14 h | 10.7 ± 6.7 h |
| Terminal half-life | 24 ± 11 h | 41 ± 14 h | 32 ± 4 h |
| Apparent clearance | Not reported | 0.86 ± 0.48 L/h | 0.90 ± 0.12 L/h |
Other points from the label:
- Absolute bioavailability after subcutaneous injection was 66 ± 39% in women.
- Absorption is slower in people with a higher body mass index (BMI).
- The label says the elimination rate depends on the absorption rate, and metabolism has not been studied in humans.
- No drug-interaction studies have been done.
For follitropin beta, the Follistim AQ label gives a half-life of 33.4 (SD 4.2) h after a single 150 IU dose in women. It also notes that the Follistim pen delivers on average 18% more drug than the older reconstituted powder given by syringe, so doses are not interchangeable one-to-one.
A half-life of roughly one to two days fits with the labeled male schedules of two or three injections a week.
Approved medical use
United States
Gonal-f (vials) is approved for (Gonal-f label):
- ovulation induction in oligo-anovulatory infertile women whose infertility is not due to primary ovarian failure;
- growing multiple follicles in ovulatory women as part of assisted reproductive technology (ART);
- induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism whose infertility is not due to primary testicular failure.
The male regimen on the label is stepwise:
| Step | Labeled detail |
|---|---|
| Before starting | Confirm azoospermia (no sperm in the semen) and hypogonadotropic hypogonadism; exclude primary testicular failure and other treatable causes |
| hCG pretreatment | hCG alone, 1,000–2,250 USP units two to three times weekly, until testosterone is normal (may take 3–6 months) |
| Add Gonal-f | 150 IU subcutaneously three times weekly, plus hCG 1,000 USP units (or the dose that keeps testosterone normal) three times weekly |
| If still azoospermic | Increase Gonal-f up to 300 IU three times weekly |
| Duration | Up to 18 months to reach adequate sperm production |
The Gonal-f RFF Redi-ject pen has only the two female indications in the US (Gonal-f RFF Redi-ject label).
Follistim AQ (follitropin beta) carries the same male indication. Its labeled male dose is 450 IU per week (225 IU twice weekly or 150 IU three times weekly) with the hCG dose that normalized testosterone. The label says improvement should not be expected for at least 3–4 months, and responses were seen at up to 12 months (Follistim AQ label).
European Union
The EU authorized Gonal-f on 20 October 1995. Its EU indications include women with severe LH and FSH deficiency (given with LH) and adult men with hypogonadotrophic hypogonadism (given with hCG) (EMA, Gonal-f). Two biosimilars of follitropin alfa, Ovaleap (September 2013) and Bemfola (March 2014), carry the same male indication with hCG (EMA, Ovaleap; EMA, Bemfola).
What the research shows
Hypogonadotropic hypogonadism: the registration trials
The US approval for men rests on three open-label, uncontrolled, escalating-dose trials in 78 men aged 16–48 with hypogonadotropic hypogonadism and azoospermia. All first had 3–6 months of hCG alone, then up to 18 months of Gonal-f plus hCG; 63 received Gonal-f. The primary endpoint was a sperm concentration of 1.5 million/mL or more (Gonal-f label):
| Outcome | Trial 1 | Trial 2 | Trial 3 |
|---|---|---|---|
| Men evaluated | 26 | 8 | 29 (25 with data) |
| Reached 1.5 million/mL or more | 12 (46%) | 5 (63%) | 20 (80% of men with data) |
| Median time to that level | 12.4 months | 9.1 months | 9 months |
| Pregnancies among partners seeking pregnancy | 6 of 7 (86%) | 3 of 10 (30%) | 5 of 26 (19%) |
A combined analysis of four phase III trials of the same regimen (Australia, Europe, Japan, US) included 100 men (Warne et al., Fertil Steril 2009). Of 81 men who were still azoospermic after hCG had normalized their testosterone:
- 68 (84.0%) began producing sperm;
- 56 (69.1%) reached 1.5 million/mL or more;
- larger testes at baseline, lower BMI and more advanced sexual maturity predicted a better response.
For follitropin beta, an open-label study randomized 30 azoospermic men (after 16 weeks of hCG) to two Follistim schedules for 48 weeks (Follistim AQ label). Overall, 13 of 30 (43%) reached at least 1 million/mL on their last two semen tests: 6 of 15 (40%) on 150 IU three times weekly and 7 of 15 (47%) on 225 IU twice weekly. Median time to that level was 165 days.
FSH plus hCG versus hCG alone
Meta-analyses pool many small, mostly uncontrolled studies, but they agree that adding FSH helps sperm output:
| Meta-analysis | Studies / men | Main findings |
|---|---|---|
| Muir et al., Clin Endocrinol 2025 | 41 / 1,673 | After a median 18 months, sperm appeared in 78%; over 1, 5, 10 and 20 million/mL in 55%, 36%, 24% and 15%. Combined hCG/FSH beat hCG alone at every threshold; testosterone and testis volume rose equally with both |
| Huijben et al., Andrology 2026 | 50 / 1,583 | Sperm induction in 74% (95% CI 66–82%), mean 11.8 months; pregnancy in 52% (95% CI 42–62%) of couples trying; dual gonadotropin therapy more effective than hCG alone |
Huijben and colleagues rated most included studies as of poor methodological quality. Muir and colleagues also found lower sperm output in men with congenital hypogonadotropic hypogonadism than in men with hypopituitarism (broader pituitary failure). The hCG page covers these outcomes from the hCG side.
FSH first, in men with prepubertal testes
In a small randomized trial, 13 men with congenital hypogonadotropic hypogonadism and very small testes (under 4 mL) received either pulsatile GnRH alone for 24 months or 4 months of recombinant FSH first (Dwyer et al., JCEM 2013):
| Measure (FSH pretreatment phase) | Before | After 4 months of FSH |
|---|---|---|
| Inhibin B (a Sertoli-cell marker) | 29 ± 9 pg/mL | 107 ± 41 pg/mL |
| Testis volume | 1.1 ± 0.2 mL | 2.2 ± 0.3 mL |
Biopsies showed more Sertoli cells and spermatogonia (sperm precursor cells). All 7 men given FSH first developed sperm, versus 4 of 6 on GnRH alone. The trial was too small to prove a difference.
Idiopathic male infertility (off-label)
In men with poor semen quality and no hormonal cause, FSH is used off-label. The evidence is suggestive but low in quality:
| Review | Design | Main findings |
|---|---|---|
| Attia et al., Cochrane 2013 | 6 RCTs, 456 men; gonadotropins vs placebo or no treatment | Spontaneous pregnancy 16% vs 7% (Peto OR 4.94, 95% CI 2.13–11.44; moderate quality). Live birth 27% vs 0% in one 30-man study (very low quality). No difference when IUI or ICSI was used |
| Santi et al., Endocr Connect 2015 | 15 controlled studies, 614 treated vs 661 controls | Spontaneous pregnancy OR ≈4.5 (95% CI 2.17–9.33); pregnancy after ART OR 1.60 (95% CI 1.08–2.37); sperm concentration +2.66 million/mL (95% CI 0.47–4.84); high risk of bias |
| Santi et al., Eur J Endocrinol 2025 | Network meta-analysis, 24 studies, 1,676 men | FSH 300 IU every other day raised sperm concentration by 9.34 million/mL (95% CI 5.14–13.53) vs placebo; clomiphene 25 mg every other day ranked higher (22.00 million/mL, 95% CI 14.75–29.25). No treatment improved progressive motility |
The AUA/ASRM male infertility guideline states that clinicians “may consider” an FSH analogue for idiopathic infertility to improve sperm concentration, pregnancy and live birth rates (Moderate Recommendation; Evidence Level Grade B) (AUA/ASRM guideline; Schlegel et al., J Urol 2021). This use is not on the US label.
After testosterone or anabolic steroid use
Testosterone and anabolic steroids shut down the pituitary’s LH and FSH output, which can stop sperm production. The AUA/ASRM guideline says clinicians should not prescribe testosterone to men interested in current or future fertility, and its discussion of hypogonadotropic hypogonadism describes hCG first, then FSH when indicated once testosterone has normalized (AUA/ASRM guideline).
There are no controlled trials of FSH for recovery after testosterone or steroid use. The main published series is retrospective:
- 49 men with azoospermia or severe oligospermia (under 1 million/mL) while on testosterone received hCG 3,000 units every other day plus clomiphene, tamoxifen, anastrozole or recombinant FSH, by physician preference (Wenker et al., J Sex Med 2015).
- 47 men (95.9%) regained sperm or improved their counts, after a mean of 4.6 months.
- Recovery did not differ by which add-on drug was used, and there was no untreated comparison group.
A 2025 review of steroid- and testosterone-induced azoospermia lists hCG and FSH among the treatment options, but stresses the “notable lack” of controlled, long-term studies in this setting (Hashimi et al., Asian J Androl 2025). Upstream options that restart the pituitary itself, such as clomiphene, enclomiphene and gonadorelin, work by a different mechanism.
Side effects and risks
In men
Across the three Gonal-f trials in men (63 treated, all also on hCG), the label lists these adverse reactions (Gonal-f label):
| Adverse reaction | Men, n (%) |
|---|---|
| Acne | 17 (27%) |
| Injection site pain | 7 (11%) |
| Fatigue | 6 (10%) |
| Gynecomastia (breast tissue growth) | 4 (6%) |
| Seborrhea | 3 (5%) |
| Decreased libido | 2 (3%) |
One man had gynecomastia serious enough to need surgical removal of breast tissue. No man stopped treatment because of side effects. Because every man was also on hCG, which raises testosterone and estradiol, these rates describe the combination rather than FSH alone. In the Follistim study (30 men), headache, injection-site reactions, injection-site pain and acne each occurred in 2 men (6.7%), and gynecomastia, rash and a dermoid cyst in 1 each (Follistim AQ label).
Allergic reactions
Serious hypersensitivity reactions, including anaphylaxis, have been reported after marketing. Symptoms included shortness of breath, facial swelling, itching and hives.
In women
Most of the label’s warnings concern women undergoing ovarian stimulation:
- Ovarian hyperstimulation syndrome (OHSS): a sudden leak of fluid from blood vessels into the abdomen and chest, which can become serious; in the US ovulation-induction trial it occurred in 6.8% of women.
- Multiple births: 20% of live births after ovulation induction and 35.1% after ART in Gonal-f trials.
- Blood clots and lung complications: thromboembolism, stroke and, rarely, death have been reported with gonadotropins.
- Ovarian torsion, ectopic pregnancy and miscarriage, the last not shown to be caused by the drug.
Who should not use it
The Gonal-f label contraindicates it in women and men with:
- prior hypersensitivity to recombinant FSH or its ingredients;
- high FSH levels indicating primary gonadal failure (the testes or ovaries themselves have failed, so more FSH cannot help);
- uncontrolled thyroid, adrenal or pituitary disorders;
- sex-hormone-dependent tumors of the reproductive tract and accessory organs;
- tumors of the pituitary or hypothalamus.
Interactions
No drug-interaction studies of follitropin alfa have been done (Gonal-f label). In men, its intended partner drug is hCG.
Legal status and use outside medicine
In the US, follitropin alfa is a prescription biologic. It is not one of the anabolic steroids listed in DEA Schedule III (21 CFR 1308.13).
The WADA 2026 Prohibited List bans “testosterone-stimulating peptides in males” under S2.2.1, “including, but not limited to” chorionic gonadotrophin, LH, GnRH and its analogues, and kisspeptin. FSH is not named. Products that also contain hCG or LH, such as hMG, fall under the named substances.
Key takeaways
- Recombinant FSH, not a hormone booster. Follitropin alfa (Gonal-f) is lab-made human FSH. It acts on the Sertoli cells that support sperm production and does not raise testosterone.
- Labeled for men only with hCG. The US label covers inducing sperm production in men with hypogonadotropic hypogonadism, at 150–300 IU three times weekly after 3–6 months of hCG alone.
- It works, slowly. In the registration trials, 46–80% of men reached 1.5 million/mL or more, typically after 9–12 months. Meta-analyses find hCG plus FSH produces more sperm than hCG alone.
- Weaker evidence elsewhere. For idiopathic male infertility, small trials suggest higher pregnancy rates, and the AUA/ASRM guideline allows it. For recovery after testosterone or steroid use, only uncontrolled case series exist.
- Main risks differ by sex. In men, acne, injection-site pain and gynecomastia were the most common reactions on FSH plus hCG. In women, OHSS and multiple pregnancy dominate the label.
Sources
- EMD Serono. Gonal-f (follitropin alfa) for injection, prescribing information. DailyMed.
- EMD Serono. Gonal-f RFF Redi-ject (follitropin alfa) injection, prescribing information. DailyMed.
- Organon. Follistim AQ Cartridge (follitropin beta) injection, prescribing information. DailyMed.
- European Medicines Agency. GONAL-f: EPAR. EMA.
- European Medicines Agency. Ovaleap: EPAR. EMA.
- European Medicines Agency. Bemfola: EPAR. EMA.
- Warne DW, Decosterd G, Okada H, et al. A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril. 2009;92(2):594–604. PubMed.
- Muir CA, Zhang T, Jayadev V, et al. Efficacy of gonadotropin treatment for induction of spermatogenesis in men with pathologic gonadotropin deficiency: a meta-analysis. Clin Endocrinol (Oxf). 2025;102(2):167–177. PubMed.
- Huijben M, Prinsen A, de Kort L, et al. Boosting male fertility: the impact of gonadotropin therapy on hypogonadotropic hypogonadism—a systematic review and meta-analysis. Andrology. 2026;14(7):1971–1987. PubMed.
- Dwyer AA, Sykiotis GP, Hayes FJ, et al. Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98(11):E1790–E1795. PubMed.
- Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2013;(8):CD005071. PubMed.
- Santi D, Granata AR, Simoni M. FSH treatment of male idiopathic infertility improves pregnancy rate: a meta-analysis. Endocr Connect. 2015;4(3):R46–R58. PubMed.
- Santi D, Pallotti F, Tienforti D, et al. Empirical hormonal treatments for idiopathic male infertility: a network meta-analysis comparing antiestrogens and FSH. Eur J Endocrinol. 2025;193(6):S95–S105. PubMed.
- Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. J Urol. 2021;205(1):44–51. PubMed; full guideline at AUA.
- Wenker EP, Dupree JM, Langille GM, et al. The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use. J Sex Med. 2015;12(6):1334–1337. PubMed.
- Hashimi MA, Pinggera GM, Shah R, et al. Clinician’s guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids. Asian J Androl. 2025;27(3):330–341. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.