• Leo Rex

Spermatogenesis, its Regulation, and Recovery

Updated: Apr 27, 2020

This blog post is part of a series on the recovery of men’s natural testosterone production and fertility after the use of anabolic and androgenic steroids.

To watch the video that accompanies this article, click here.

In the bodybuilding world, Dave Palumbo and Bostin Lloyd are well known for their effective ‘pregnancy protocols,’ which both prescribe the use of human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG), and clomiphene citrate (CC). Nonetheless, I frequently receive questions from clients and viewers of my YouTube channel on how one can recover endogenous testosterone production and fertility after the use of anabolic and androgenic steroids (AAS). In this series of blog posts, I will provide an overview of natural spermatogenesis and its regulation and I will describe the tools that can be used to aid in recovery. In the final article, and for educational purposes only, I will speculate on an ideal program.


In normal physiology, the brain’s hypothalamus releases gonadotropin-releasing hormone (GnRH) in a pulsatile fashion via the portal system. When GnRH reaches the pituitary gland, the pituitary in turn releases the gonadotropins. Astute performance enhancement aficionados will note that these are the same parts of the brain involved in growth hormone production. In this case, they form an axis called the hypothalamus-pituitary-gonadal (HPG) axis.

The critical gonadotropins released by the pituitary are luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates Leydig cells in the testis to produce testosterone. This leads to an increase in intratesticular testosterone (ITT) and also increases insulin-like growth factor (IGF-1) production in the testes. Testicular IGF-1 regulates Leydig cell LH receptor upregulation, steroidogenesis, and maturation[1]. In addition to LH, the pituitary gland produces FSH, which stimulates Sertoli cells in the testis to promote spermatogonial differentiation and maturation.

Both FSH and ITT, resulting from LH, are needed for spermatogenesis. While the absence of FSH impairs spermatogenesis, the loss of ITT due to a lack of LH will totally inhibit spermatogenesis[2].


Spermatogenesis is regulated by a multiplicity of factors, including less well-understood autocrine, paracrine, and endocrine factors such as endocannabinoids, interleukins, norepinephrine, and TGF-β[3]. Nonetheless, for the purposes of fertility, the feedback inhibition of spermatogenesis governed by testosterone and estrogen are most concerning.

Endogenous testosterone production provides feedback to the HPG system. As it rises, it inhibits GnRH release in the hypothalamus, thereby inhibiting LH from the pituitary. Estrogen, having been aromatized from testosterone, inhibits both LH and FSH from the pituitary, although it inhibits LH with greater effect.

Note that FSH is also inhibited by inhibin B, secreted directly from the Sertoli cells in the testis.


Anabolic and androgenic steroids (AAS) mimic the natural feedback mechanism that halts endogenous testosterone production and spermatogenesis by binding to androgen receptors and converting to estrogen. This leads to reductions in serum gonadotropins and in intratesticular testosterone (ITT)[4]. Though the matter is not studied sufficiently, it appears that dose and the number of compounds used further complicates recovery from AAS[5][6]. It is tempting to speculate that the greater the affinity of the steroid for the androgen receptor and the greater the serum estrogen level, the more the HPG axis will be impaired as a result of AAS use.


I have reviewed the academic literature extensively. Most studies are performed on people who naturally had issues with fertility. These studies are less applicable to users of anabolic and androgenic steroids, partly because not experiencing puberty naturally greatly impairs future spermatogenesis.

The most studies of drug-related effects on fertility have been done on male contraception, and these indicate 67% of people recover in 6 months, 90% recover in 12 months, and 100% recover in 24 months without therapy[7]. With that said, the few studies involving anabolic and androgenic use indicate that some patients require longer periods to recover, even with therapy. Note that prolonged exposure to testosterone replacement therapy, age, and East Asian ethnicity are factors that complicate recovery[8].

To read the next article in this series, click here.

[1] Wang, G., & Hardy, M. P. (2004). Development of leydig cells in the insulin-like growth factor-I (igf-I) knockout mouse: effects of igf-I replacement and gonadotropic stimulation. Biology of Reproduction, 70(3), 632-639. [2] Kumar, T. R. (2005). What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?. Reproduction, 130(3), 293-302. [3] McBride, J. A., & Coward, R. M. (2016). Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian journal of andrology, 18(3), 373. [4] Jarow, J. P., & Lipshultz, L. I. (1990). Anabolic steroid-induced hypogonadotropic hypogonadism. The American journal of sports medicine, 18(4), 429-431. [5] Rahnema, C. D., Lipshultz, L. I., Crosnoe, L. E., Kovac, J. R., & Kim, E. D. (2014). Anabolic steroid–induced hypogonadism: diagnosis and treatment. Fertility and sterility, 101(5), 1271-1279. [6] Evans, N. A. (2004). Current concepts in anabolic-androgenic steroids. The American Journal of Sports Medicine, 32(2), 534-542. [7] Liu, P. Y., Swerdloff, R. S., Christenson, P. D., Handelsman, D. J., & Wang, C. (2006). Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. The Lancet, 367(9520), 1412-1420. [8] McBride, J. A., & Coward, R. M. (2016). Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian journal of andrology, 18(3), 373.

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