Testosterone Cypionate and Fertility Suppression: When to Call Your Doctor

What testosterone cypionate does to sperm production

The Depo-Testosterone label describes the mechanism in a sentence: during exogenous androgen administration, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone, and at large doses spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle-stimulating hormone [1]. The same label lists oligospermia, a low sperm count, among the reactions that may occur at high dosages, and its drug abuse section lists testicular atrophy, subfertility and infertility among reactions reported in men who abuse anabolic steroids [1].

A 2013 review states that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis [7]. In a study of 29 healthy men, the group given weekly 200 mg testosterone enanthate plus placebo had intratesticular testosterone fall by 94% [8].

In one fertility-clinic series, 59 of 4,400 men (1.3%) presenting for a fertility evaluation reported taking testosterone, and 88.4% of those men were azoospermic, meaning no sperm in the ejaculate, while on it [4]. These were men who came to a fertility clinic, so the figure does not describe all men on testosterone.

Situations that call for fertility evaluation

Before the first injection, if a pregnancy is planned in the near term. The Endocrine Society guideline recommends against starting testosterone therapy in men planning fertility in the near term [2]. For men whose low testosterone comes from a pituitary or hypothalamic problem, one review describes withdrawing testosterone and using gonadotropins when fertility is the goal [10].

When a semen analysis shows azoospermia or severe oligospermia. One treatment series used a threshold of under 1 million sperm/mL to define severe oligospermia [3]. That result is what opens the treatment options described below.

When sperm counts stay low during fertility treatment. In one series of 66 men given high-dose hCG plus a selective estrogen receptor modulator after testosterone, 46 (70%) reached a total motile count above 5 million within 12 months. Only 64.8% of the men who started azoospermic reached that count, compared with 91.7% of men with cryptozoospermia, meaning sperm present in very small numbers [6].

When testosterone has been used for years and children are only now being considered. In the same series, longer prior testosterone use and older age both predicted a longer time to sperm recovery at 6 and 12 months [6].

What can be done to protect or restore sperm production

hCG alongside testosterone. In a retrospective review of 26 hypogonadal men who stayed on testosterone (19 on injections, 7 on gel) and added hCG 500 IU every other day, no patient became azoospermic, semen parameters did not change over more than a year of follow-up, and 9 of the 26 men contributed to a pregnancy with their partner [13]. That review had no comparison group. In a randomized study of 29 men with normal reproductive function, 200 mg testosterone enanthate weekly plus hCG every other day for 3 weeks raised intratesticular testosterone in step with the hCG dose: 125 IU left it 25% below baseline, 250 IU left it 7% below, and 500 IU put it 26% above baseline, while testosterone alone cut it by 94% [8]. That study measured intratesticular testosterone, not sperm counts, and ran for three weeks.

hCG-based recovery. In a retrospective series of 49 men with azoospermia or severe oligospermia while on testosterone, treatment with hCG 3,000 units injected under the skin every other day plus clomiphene, tamoxifen, anastrozole or recombinant FSH was followed by a return of spermatogenesis or improved counts in 47 men (95.9%), at an average of 4.6 months, with a mean first sperm density of 22.6 million/mL. Recovery did not differ by the type of testosterone used [3].

SERMs instead of testosterone. A 2013 review describes clomiphene citrate as effective for maintaining testosterone production and as a well-tolerated oral option for men who want to keep future fertility, and describes hCG with or without testosterone as an alternative [7]. A 2014 review of anabolic steroid-induced hypogonadism lists careful testosterone replacement, hCG and selective estrogen receptor modulators as management options, and notes that no studies of sufficient quality met its criteria for meta-analysis [11].

The recovery series are retrospective and have no control group, so the percentages describe what happened in those clinics rather than a tested success rate [3][6].

How long does recovery take?

The largest recovery dataset comes from hormonal male contraception research rather than from men with hypogonadism. An integrated analysis of 30 studies covering 1,549 healthy men with normal fertility on androgen or androgen-progestin regimens found a median of 3.4 months for sperm concentration to return to 20 million/mL; the recovery probability was 67% within 6 months, 90% within 12 months, 96% within 16 months and 100% within 24 months in that population [5]. Recovery was faster with shorter-acting testosterone, shorter treatment, older age and a higher baseline sperm count [5].

Data from men who took testosterone for low testosterone is thinner. In one clinic series, 65% of men without another known cause for azoospermia recovered spermatogenesis within 6 months of stopping [4]. In the 66-man hCG plus SERM series, 70% reached a total motile count above 5 million within 12 months, and older age and longer testosterone use slowed recovery [6].

The two datasets point in opposite directions on age: the contraception analysis found faster recovery in older men, while the treatment series found that age limited recovery [5][6]. They studied different groups, healthy fertile men in one and men treated for infertility in the other, and neither was a controlled trial.

What a semen analysis shows

A semen analysis turns the question of suppression into a number. In a 2021 analysis pooling data from more than 3,500 men in 12 countries, the 5th centile values for fertile men were 16 million sperm/mL, 30% progressive motility and 4% normal forms [12]. Those values describe fertile men; they are not a strict cut-off between fertile and subfertile [12].

Two terms come up repeatedly. Azoospermia means no sperm in the ejaculate. Severe oligospermia means a very low count; one of the treatment series used under 1 million sperm/mL [3].