What Is FSH (Follitropin Alfa)?

1. What is follitropin alfa, and how does it differ from other FSH products?

FSH is built from two protein chains. The Gonal-f prescribing information describes an alpha chain of 92 amino acids and a beta chain of 111, a structure it calls indistinguishable from the body’s own FSH, and a molecular weight of about 31 kDa.

Before recombinant products, fertility FSH was purified from the urine of postmenopausal women, as in menotropins (hMG), which supplies both FSH and LH activity. A recombinant product carries FSH activity only. That is the practical reason the labels pair it with hCG in men: something else has to supply the testosterone signal.

The two labels describe the same chain lengths but list different molecular weights for the finished proteins. The Follistim label also reports that its pen gives, on average, 18% more drug than the earlier powder injected by syringe, so units from different products and devices cannot be swapped one-for-one.

2. How does FSH work in men?

The testis runs on two pituitary signals. LH drives the Leydig cells to make testosterone. FSH acts on the Sertoli cells, often described as nurse cells, which hold and feed sperm as they mature. According to the Follistim label, spermatogenesis, the medical term for sperm production, is the process FSH is chiefly responsible for.

The AUA/ASRM male infertility guideline notes that without LH and FSH stimulation, the Leydig cells stop secreting testosterone and sperm production is disrupted. When the pituitary stops releasing both hormones, both signals have to be replaced from outside.

Direct tissue evidence comes from Dwyer and colleagues’ randomized trial, in which testicular biopsies from men given recombinant FSH showed more Sertoli cells and more spermatogonia, the precursor cells that become sperm.

FSH is not a testosterone booster

Muir and colleagues’ 2025 meta-analysis pooled 41 studies of men with gonadotropin deficiency. Testosterone and testis volume increased to the same extent whether men received hCG alone or hCG plus FSH. The only outcome that clearly favored the combination was sperm output. We found no trial showing that FSH builds muscle.

3. What did the trials in men show?

The US registration trials

The male indication in the US is based on three uncontrolled, open-label studies of 78 men aged 16 to 48 with hypogonadotropic hypogonadism and no sperm in their semen (azoospermia). Each man first took hCG alone for 3 to 6 months, then up to 18 months of Gonal-f plus hCG; 63 men received Gonal-f. Success was defined as a sperm concentration of at least 1.5 million/mL, according to the Gonal-f label.

Warne and colleagues combined four phase III trials of this regimen, run in Australia, Europe, Japan and the US, covering 100 men. Of the 81 men who remained azoospermic even once hCG had brought testosterone into the normal range, 68 (84.0%) began producing sperm and 56 (69.1%) reached 1.5 million/mL. Men did better if they started with bigger testes, a lower BMI or a later stage of sexual maturation.

For follitropin beta, the Follistim AQ label describes 30 men randomized after 16 weeks of hCG to 150 IU three times weekly or 225 IU twice weekly for 48 weeks. On the final two semen samples, 13 of 30 men (43%) had at least 1 million/mL, 6 of 15 and 7 of 15 in the two groups, with a median time of 165 days.

Does adding FSH beat hCG alone?

Two meta-analyses agree that it does for sperm, though both pool mostly small, uncontrolled studies:

Huijben’s team judged most included studies to be of poor methodological quality. Muir’s team also reported that men born with hypogonadotropic hypogonadism produced less sperm than men with hypopituitarism, a broader failure of the pituitary gland. The hCG guide looks at these same outcomes from the hCG side.

Giving FSH first in men with very small testes

In Dwyer and colleagues’ trial, 13 men with congenital hypogonadotropic hypogonadism and testes under 4 mL were randomized to pulsatile GnRH alone for 24 months or to 4 months of recombinant FSH beforehand.

All 7 men in the FSH-first group developed sperm, compared with 4 of 6 on GnRH alone. With 13 participants, the study could not prove that the difference was real.

4. Off-label uses: idiopathic infertility and recovery after steroids

Low sperm counts without a hormone problem

When no hormone problem explains low sperm counts, the infertility is called idiopathic. FSH is sometimes used here outside its label, and the evidence is suggestive but weak:

The Cochrane review also reported a live-birth rate of 27% versus 0% in a single 30-man study, rated very low quality. The AUA/ASRM guideline, summarized by Schlegel and colleagues, says clinicians “may consider” an FSH analogue in idiopathic infertility (Moderate Recommendation; Evidence Level Grade B). That use is not on the US label.

After testosterone or anabolic steroid use

External testosterone and anabolic steroids suppress the pituitary’s LH and FSH output, which can halt sperm production. The AUA/ASRM guideline advises against prescribing testosterone to men who want current or future fertility, and for hypogonadotropic hypogonadism it describes starting with hCG and adding FSH once testosterone has normalized, when indicated.

No controlled trial has tested FSH in this setting. In Wenker and colleagues’ retrospective series, 49 men with no sperm or severely low counts while on testosterone received hCG 3,000 units every other day plus clomiphene, tamoxifen, anastrozole or recombinant FSH, chosen by the physician. Forty-seven (95.9%) regained sperm or improved counts after a mean of 4.6 months, but outcomes did not differ by add-on drug and nobody went untreated for comparison.

Hashimi and colleagues’ 2025 review lists hCG and FSH among treatment options for steroid-induced azoospermia while stressing the shortage of controlled, long-term studies. Kisspeptin, which WADA groups with hCG as a testosterone-stimulating peptide, is a separate research compound covered in the kisspeptin-10 guide; none of the studies above included it.

5. Is FSH approved, and is it legal?

United States

Gonal-f vials carry three US indications: ovulation induction in women whose infertility is not due to primary ovarian failure, developing multiple follicles during assisted reproduction, and inducing sperm production in men with primary or secondary hypogonadotropic hypogonadism whose infertility is not due to primary testicular failure. The Redi-ject pen has only the two female indications.

Follitropin alfa is a prescription biologic. It is not among the anabolic steroids listed in Schedule III under 21 CFR 1308.13.

European Union

Gonal-f received EU authorization on 20 October 1995. In Europe it is indicated, among other uses, for women with severe deficiency of both LH and FSH (combined with LH) and for adult men with hypogonadotrophic hypogonadism (combined with hCG), according to the EMA’s Gonal-f page. The biosimilars Ovaleap, authorized in September 2013, and Bemfola, authorized in March 2014, carry the same male indication.

Sport

Section S2.2.1 of the WADA 2026 Prohibited List prohibits peptides that stimulate testosterone in men, “including, but not limited to” chorionic gonadotrophin, LH, GnRH and its analogues, and kisspeptin. FSH is not named. In practice, men receive FSH together with hCG, which is named.

6. How is FSH dosed in men, according to the labels?

The doses below are the labeled regimens for diagnosed hypogonadotropic hypogonadism, prescribed and monitored by a specialist. They are not a template for other uses.

The Follistim AQ label sets 450 IU per week for men, as 225 IU twice weekly or 150 IU three times weekly, with the hCG dose that normalized testosterone. It warns that benefit is unlikely to show before 3 to 4 months, and responses were seen up to 12 months.

Half-life and absorption

These values come from the Gonal-f label after subcutaneous injection:

Absolute bioavailability after subcutaneous injection was 66 ± 39% in women, a wide spread. The label also reports slower absorption at a higher BMI and says elimination depends on the absorption rate; human metabolism has not been studied. For follitropin beta, the Follistim label gives a single-dose half-life of 33.4 hours in women.

A half-life of one to two days fits the two- or three-times-weekly schedules. A half-life curve shows how blood levels fall between injections, but FSH’s effect on sperm builds over months, so the curve says little about how long a benefit lasts.

7. What are the side effects and risks?

In men

Every man in the Gonal-f trials was also taking hCG, which raises testosterone and estradiol, so the figures reflect the pair of drugs, not FSH in isolation:

One man’s gynecomastia was severe enough to need surgery, and none of the men quit because of adverse effects. In the 30-man Follistim study, headache, injection-site reactions, injection-site pain and acne each affected 2 men (6.7%). Serious allergic reactions, including anaphylaxis, have been reported since marketing.

In women

The label’s major warnings concern ovarian stimulation. Ovarian hyperstimulation syndrome (OHSS), in which fluid shifts out of blood vessels into the abdomen and chest, occurred in 6.8% of women in the US ovulation-induction trial. Multiple births made up 20% of live births after ovulation induction and 35.1% after assisted reproduction, and blood clots, stroke and ovarian torsion have been reported with gonadotropins.

Contraindications

The Gonal-f label lists these contraindications for both sexes:

• hypersensitivity to recombinant FSH or any ingredient;
• high FSH levels that indicate primary gonadal failure, where the testes or ovaries themselves no longer respond;
• uncontrolled thyroid, adrenal or pituitary disease;
• sex-hormone-dependent tumors of the reproductive tract or accessory organs;
• pituitary or hypothalamic tumors.

8. Interactions, including GLP-1 medicines

According to the Gonal-f label, follitropin alfa has never been formally studied for drug interactions. That includes semaglutide, tirzepatide and other GLP-1 drugs: there are no data showing either a problem or the absence of one. In men, the drug FSH is designed to be used with is hCG.

Two weight-related findings are documented, without a causal link to weight loss. The label reports slower absorption at a higher BMI, and in Warne’s combined analysis, lower BMI was one of the factors that predicted a better sperm response. Neither study tested whether losing weight during treatment changes the outcome.

9. What can you actually measure?

Because FSH and hCG act on different targets, each has its own marker. Mixing them up is the most common way to misread a result.

Time scales matter when reviewing a log. Median times to the sperm threshold were 9 to 12 months in the registration trials, so a semen test after a few weeks cannot judge the treatment. Recording injection dates, product, dose, every lab result with its date and any side effects, such as acne or breast tenderness, gives a clinician a usable timeline. The peptide tracking guide covers ways to keep those records together.

10. FSH FAQ

• Does FSH increase testosterone?

  No. FSH acts on Sertoli cells, not on the Leydig cells that make testosterone. A 2025 meta-analysis of 41 studies found that testosterone and testis volume rose by the same amount with hCG alone and with hCG plus FSH; only sperm output was higher with the combination.

• What is follitropin alfa used for in men?

  In the US, Gonal-f vials are labeled for inducing sperm production in infertile men with hypogonadotropic hypogonadism, meaning low testosterone and absent sperm caused by pituitary or hypothalamic failure. It is used with hCG and is not labeled for men whose testes themselves have failed.

• Is FSH legal, and is it banned in sport?

  In the US it is a prescription biologic and is not on the DEA's Schedule III list of anabolic steroids. FSH is not named on the WADA 2026 Prohibited List, but hCG, which men receive alongside it, is named under S2.2.1, and that section's wording is not limited to the substances it lists.

• What are the side effects of FSH in men?

  In the Gonal-f trials in men, all of whom also took hCG, the most common reactions were acne (27%), injection-site pain (11%), fatigue (10%) and gynecomastia (6%). Serious allergic reactions, including anaphylaxis, have been reported after marketing.

• How long does FSH stay in your system?

  The Gonal-f label reports a terminal half-life of 41 ± 14 hours after a single injection in healthy men and 32 ± 4 hours after a week of daily injections. Half-life describes how blood levels fall; it does not say how long effects on sperm production last.

• How long does FSH take to work?

  Slowly. In the US registration trials, median time to a sperm concentration of at least 1.5 million/mL was about 9 to 12 months, and the label allows up to 18 months of combined treatment. The follitropin beta label says not to expect improvement for at least 3 to 4 months.

• Can FSH be used with semaglutide or tirzepatide?

  No study has tested that combination, and the Gonal-f label states that no drug-interaction studies have been done at all. Anyone combining treatments should tell each prescriber about every medicine. The label does note that absorption of follitropin alfa is slower at a higher BMI.

• Does FSH help recovery after steroids or TRT?

  There are no controlled trials. The main published series gave hCG plus one of several add-on drugs, including FSH in some men, and most regained sperm, but recovery did not differ by add-on and there was no untreated comparison group.

11. Sources