Any testosterone introduced from the outside is perceived by the body as a "hormone enough" signal. In response, it reduces its own production—and this applies to testosterone propionate as well as other esters. The editors explain how the hypothalamic-pituitary-testicular axis works, what happens to it under the influence of exogenous androgens, and what is known about recovery after their withdrawal.
How the HPT axis works
The hypothalamic-pituitary-testicular axis (HPT) is a three-link system that regulates testosterone production and spermatogenesis. The hypothalamus releases gonadotropin-releasing hormone (GnRH) in pulses, approximately every 1–2 hours. In response, the pituitary gland secretes two gonadotropins — luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
LH acts on Leydig cells in the testes, stimulating the synthesis of testosterone from cholesterol. FSH together with a high local concentration of testosterone inside the testicle supports the functioning of Sertoli cells and the maturation of spermatozoa. It is important that the concentration of testosterone inside the testicles is many times higher than in the blood, and it is precisely this concentration that is needed for normal spermatogenesis.
The system works on the principle of negative feedback, like a thermostat. When blood levels of testosterone and estradiol increase, the hypothalamus and pituitary gland decrease the production of GnRH, LH, and FSH. When the level drops, the stimulation increases. In addition, Sertoli cells produce inhibin B, which selectively inhibits FSH secretion.
This mechanism ensures the stability of the hormone level in a healthy man. But this same mechanism makes the system vulnerable to exogenous testosterone: the body does not distinguish between "own" and "introduced" hormone and reacts to the total concentration.
Mechanism of suppression by exogenous testosterone
After an injection of testosterone propionate, the level of testosterone in the blood rises rapidly, and with it the level of estradiol, which is formed by aromatization. Both hormones increase the inhibition of the hypothalamus and pituitary gland. As a result, the frequency and amplitude of GnRH pulses, as well as the secretion of LH and FSH, decrease.
Without LH stimulation, Leydig cells reduce the synthesis of their own testosterone. At the same time, the level of testosterone in the blood can remain high or even supraphysiological - but due to the injected drug. At the same time, the intratesticular concentration of testosterone drops sharply, because the external hormone does not create the high concentrations in the testicles that are provided by its own synthesis.
The degree of inhibition depends on the dose, duration and frequency of administration. For a short ester, such as propionate, repeated peaks of concentration after injections are characteristic. Even at relatively moderate doses, total inhibition of the axis can be significant, especially with long-term use.
This is not a "side effect" in the usual sense, but a natural physiological response. It is this mechanism that has been studied as the basis of male hormonal contraception: in WHO studies, weekly injections of testosterone enanthate inhibited spermatogenesis in most healthy men.
- Increase of testosterone and estradiol in the blood.
- Reduction of GnRH secretion by the hypothalamus.
- LH and FSH drop to low or undetectable levels.
- Reduction of own testosterone synthesis and intratesticular concentration.
- Violation of spermatogenesis up to azoospermia.
Implications for testes and fertility
The most noticeable external sign of axis suppression is a reduction in testicular volume. The spermatogenic epithelium accounts for the majority of this volume, and it undergoes atrophy in the absence of stimulation by FSH and intratesticular testosterone. These changes typically develop over the course of weeks or months of use.
Concurrently, the sperm count in the ejaculate decreases, progressing to oligospermia or complete azoospermia. In a WHO contraceptive study (1990), the majority of participants receiving testosterone enanthate developed azoospermia within a few months. However, as spermatogenesis was not completely suppressed in some men, testosterone is not considered a reliable standalone contraceptive.
A review by Ohlander et al. (2016) in *Urologic Clinics of North America* highlights a paradox: men seeking infertility treatment are sometimes already taking testosterone, unaware that it may be the very cause of the problem. Therefore, before planning to have children, physicians routinely check whether androgens are being used.
For men planning to have children, this is a crucial issue. The Endocrine Society clinical guidelines (2018) explicitly state that testosterone should not be prescribed to men planning to conceive in the near future, and that other approaches are considered for treating hypogonadism in such situations.
| Parameter | Baseline (normal) | During exogenous testosterone use | After discontinuation |
|---|---|---|---|
| LH | Within normal range | Low, often undetectable | Gradual recovery |
| FSH | Within normal range | Low | Gradual recovery |
| Blood testosterone | Normal | Depends on the drug; often high | May remain low for weeks or months |
| Testicular volume | Normal | Reduced | Recovers alongside FSH |
| Spermatogenesis | Normal | Oligospermia / azoospermia | Usually recovers over months |
Recovery after discontinuation
After stopping testosterone propionate, drug levels in the blood drop relatively quickly due to the short ester chain. However, the HPT axis does not "switch on" instantly; the hypothalamus and pituitary gland require time to restore normal secretion, and the testes need time to respond to it. During this interval, an individual may experience low testosterone levels.
A pooled analysis by Liu et al. (2006), published in *The Lancet*, combined data from studies on hormonal male contraception. Spermatogenesis recovered in the vast majority of participants, with a median recovery time of several months. Recovery was faster in younger men and in those who had experienced shorter periods of suppression.
However, these data were obtained under controlled conditions using moderate doses in carefully selected healthy volunteers. For actual anabolic steroid users—who often employ high doses, multiple substances, and prolonged cycles—recovery can be significantly slower. Rahnema et al. (2014) describe cases of persistent post-steroid hypogonadism.
The recovery period is often accompanied by symptoms of androgen deficiency, such as fatigue, reduced libido and erectile function, depressed mood, and loss of muscle mass. It is precisely these symptoms that often drive people to return to steroid use, creating the vicious cycle of dependence described by Kanayama and Pope.
Diagnosis and medical care
To assess the status of the HPT axis, the physician orders tests for morning total testosterone, LH, FSH, estradiol, and SHBG, as well as prolactin if necessary. A semen analysis is performed to evaluate fertility. Results are interpreted with consideration of the time elapsed since the last injection.
Low testosterone levels combined with low or normal LH and FSH levels following androgen discontinuation indicate secondary (central) hypogonadism, a condition characteristic of the post-steroid state. Conversely, if LH and FSH levels are high while testosterone is low, this may indicate testicular damage, shifting the diagnostic focus in a different direction.
Treating post-steroid hypogonadism is a task for an endocrinologist or andrologist. The choice of approach depends on the severity of symptoms, the desire to have children, the duration of androgen use, and test results. Attempts to "restart" the axis on one's own using medication—without prior diagnosis—can be ineffective and dangerous.
It is also important to assess other potential consequences of steroid use: hematocrit levels, lipid profiles, liver function, blood pressure, and psychological state. An open discussion with a doctor about drug use is essential for an accurate diagnosis, and the doctor is bound by medical confidentiality.
Editorial Conclusions
The suppression of endogenous testosterone production is an inevitable physiological response to any exogenous testosterone, including propionate. The HPT axis (hypothalamus-pituitary-testes axis) responds to the total level of androgens and estrogens without distinguishing their source.
Consequences include reduced LH and FSH levels, testicular shrinkage, impaired spermatogenesis, and temporary infertility. The short-acting propionate ester does not protect against these changes.
Recovery after discontinuation is usually possible but may take months, and for some individuals, it remains incomplete. The rate of recovery depends on age, dosage, and duration of use; therefore, the prognosis varies by individual.
The editorial team also recommends reviewing the following materials: "Tests to Monitor During Testosterone Propionate Use," "Estrogenic and Progestagenic Activity of Testosterone Propionate," and "Side Effects of Testosterone Propionate: A Comprehensive Overview of Risks."
References
- Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271â1279.
- World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet. 1990;336(8721):955â959.
- Liu PY, Swerdloff RS, Christenson PD, et al. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412â1420.
- Ohlander SJ, Lindgren MC, Lipshultz LI. Testosterone and male infertility. Urol Clin North Am. 2016;43(2):195â202.
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715â1744.
- Kanayama G, Pope HG Jr. History and epidemiology of anabolic androgens in athletes and non-athletes. Mol Cell Endocrinol. 2018;464:4â13.
- Nieschlag E, Behre HM, Nieschlag S (eds). Testosterone: Action, Deficiency, Substitution. 4th ed. Cambridge University Press; 2012.
