Human chorionic gonadotropin (hCG)

hCG is the hormone that the placenta makes in early pregnancy. It binds the same receptor as luteinising hormone (LH) but lasts far longer in the blood, so a few injections a week can stand in for LH, which would need several injections a day [1]. It has been used for more than seven decades to start puberty and sperm production in men with gonadotropin deficiency and to trigger ovulation in infertile women [1].

Men without their own gonadotropins. In a classic 1985 study of 21 men with hypogonadotropic hypogonadism, hCG alone brought sperm counts into the normal range in all 6 whose hypogonadism began after puberty, but in only 1 of 15 whose hypogonadism began before it. Adding human menopausal gonadotropin (an FSH source) then normalised counts in 5 of 7 men without a history of undescended testes and in 1 of 7 with one [6]. In a pooled analysis of four trials, 81 men stayed azoospermic after 3–6 months of hCG; once recombinant FSH was added, 84% produced sperm and 69% reached at least 1.5 million/mL. Larger testes at the start, lower BMI and more advanced puberty predicted success [7]. Once sperm production had been started, hCG alone kept sperm in the ejaculate of 12 of 13 men for up to two years, although counts drifted down without FSH [8].

Low testosterone. In a 3-month randomised trial of 282 men with hypogonadism who wanted to stay fertile, clomiphene 50 mg, hCG 5,000 IU twice weekly, and the two combined raised testosterone equally, from a mean of 2.3 to 5.2 nmol/L. Symptom scores improved most with the combination [9]. A 2025 meta-analysis found higher testosterone with clomiphene or enclomiphene than with hCG alone [10]. A review argues that hCG suits men with secondary hypogonadism who want to stay fertile, because it raises testosterone without suppressing sperm production as testosterone therapy does [11].

Keeping fertility on testosterone. Testosterone injections shut down LH and cut testosterone inside the testes by about 94%, even while blood levels are high [3]. In healthy men given 200 mg of testosterone enanthate weekly for 3 weeks, adding 125, 250 or 500 IU of hCG every other day raised intratesticular testosterone in step with the dose, from 25% below baseline at 125 IU to 26% above it at 500 IU [3]. A later trial found an effect at doses as low as 60 IU every other day [4]. Neither study measured sperm. In a retrospective series of 26 men taking testosterone with 500 IU of hCG every other day, semen parameters did not change over up to a year and nobody became azoospermic; 9 fathered pregnancies [12].

After anabolic steroids. Reviews recommend stopping the steroids and, if sperm do not return, using hCG with or without FSH or a SERM; they note there are no controlled trials in this group [13][14][15].

Ovulation trigger. In IVF, a single injection of hCG mimics the LH surge that matures the eggs. A Cochrane review of 18 trials found no difference between recombinant and urinary hCG in live birth or ovarian hyperstimulation syndrome (OHSS) [2].

Weight loss. The "Simeons" diet pairs daily hCG injections with a very-low-calorie diet. A 1995 meta-analysis of 24 trials found that only one of the 12 better-quality studies reported a benefit, and concluded that hCG does not cause weight loss, redistribute fat or reduce hunger [5]. Double-blind trials in 51, 202 and 40 people found no difference from placebo injections [16][17][18].

hCG activates the LH receptor on the Leydig cells of the testis, which then make testosterone [1]. Testosterone inside the testis is normally more than a hundred times higher than in the blood, and spermatogenesis depends on it [4]. Because hCG acts directly on the testis, it keeps intratesticular testosterone up even when the pituitary has been shut down by testosterone injections or a GnRH antagonist [3][4]. It does not replace FSH, which drives the Sertoli cells: in men on hCG alone, FSH stayed undetectable and sperm counts slowly fell [8].

Part of the extra testosterone is converted to oestradiol, which rose after single doses in healthy men [19]. In women, hCG acts on the LH receptors of the ovarian follicle to complete egg maturation, and it raised 17-hydroxyprogesterone within 36 hours [20].

Urinary hCG (Pregnyl) is purified from pregnancy urine and dosed in bioassay units; recombinant hCG (choriogonadotropin alfa, Ovidrel) is dosed by weight [1]. In men, 62.5 µg of recombinant hCG and 1,500 IU of urinary hCG gave statistically indistinguishable testosterone peaks and exposure, although the two were not formally bioequivalent for serum hCG itself [1]. Recombinant hCG was licensed only for women, so there was no evidence-based dosing for men until that trial [1].

Route matters in heavier people: subcutaneous injection produced much lower hCG levels in obese women than in normal-weight women, while intramuscular injection did not. A standard 1.5-inch needle failed to reach muscle in 36% of the obese women [20].

In single-dose studies in healthy men there were no clinical or laboratory adverse effects [1], and in the very-low-dose trial there were no serious adverse events [4]. The side effects that follow from the mechanism come from the testosterone and oestradiol it raises. hCG increased oestradiol in men [19], and a clinical guide advises checking the testosterone-to-oestradiol ratio in men who develop breast enlargement [14].

In IVF the main risk is ovarian hyperstimulation syndrome; recombinant and urinary hCG did not differ in OHSS rates, and injection-site reactions were the most common other adverse effect [2].

hCG is detected by sports drug testing; one of the trials here was partly run to calibrate the anti-doping assay, and participants were warned it could show up in workplace drug tests [1].

hCG is routinely combined with an FSH source such as Human menopausal gonadotropin (hMG) when hCG alone does not start sperm production [6][7]. In one trial it was combined with clomiphene, a close relative of Enclomiphene, without new safety problems and with a larger improvement in symptoms [9].