Home Body Building Supplements Steroids and Fertility: The Facts – T NATION+ – COMMUNITY

Steroids and Fertility: The Facts – T NATION+ – COMMUNITY

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Steroids and Fertility: The Facts – T NATION+ – COMMUNITY


AAS, TRT, and Making Babies

Can men using anabolic steroids make babies? What about TRT? If there’s a decrease in fertility, can it be restored? Here’s the science.


Testosterone and other anabolic-androgenic steroids (AAS) work, but they do have side effects. One is decreased fertility. In some cases, this persists even after discontinuation.

Post-cycle therapy (PCT) utilizing various agents and protocols can restore normal endogenous testosterone production and fertility. However, there hasn’t been much focus in the scientific literature on maintaining fertility during AAS use, whether we’re talking about testosterone replacement therapy (TRT) or supraphysiological doses of T or other steroids (abuse).

Before we delve into the data, let’s cover some basics.

The Roles of LH and FSH

Regarding sperm production, lutenizing hormone (LH) from the anterior pituitary binds to the LH receptors of the Leydig cells of the testicles, stimulating intra-testicular testosterone (ITT) production. This increase in ITT, along with follicle-stimulating hormone (FSH) binding to the Sertoli cells of the testicles, allows for the production of normal, healthy sperm.

When steroids are introduced, they activate negative feedback in the hypothalamus and pituitary, ultimately decreasing LH and FSH. This, in turn, lowers sperm production and endogenous testosterone production.

Ancillary Medications

1. Gonadotropic Hormones

Human Chorionic Gonadotropin (hCG)

This is a placental hormone produced by pregnant women which has enough molecular similarity to LH to produce the same signaling in target tissues such as the Leydig cells of the testicles. Commercial versions are derived from the purified urine of pregnant women or through recombinant DNA technology. Although not used as frequently as hCG, recombinant LH is also available.

FSH

This is a pituitary hormone necessary for sperm production via binding to and activation of FSH receptors of the Sertoli cells of the testicles. Commercial versions are derived from menopausal human urine, both highly purified to yield mainly FSH or, alternatively, a less purified version (i.e., human menopausal gonadotropin or hMG) containing LH. There’s also a version derived via recombinant DNA technology.

2. Antiestrogens

Selective Estrogen Receptor Modulators (SERMS)

Clomiphene and tamoxifen are examples. These compounds bind to and antagonize estrogen receptors in the hypothalamus and pituitary, inhibiting the negative feedback effect of estradiol. This causes a release of GnRH (gonadotropin-releasing hormone) in the hypothalamus, which consequently causes a release of both LH and FSH from the pituitary.

Aromatase Inhibitors

Examples include anastrozole and letrozole. These compounds inhibit the aromatase enzyme necessary for converting testosterone to estradiol, ultimately inhibiting estradiol-mediated negative feedback, causing increased GnRH. This, in turn, causes the anterior pituitary to release LH/FSH.

Juicing Without Ancillary Medications

While there isn’t much direct study outside of case reports for AAS use/abuse, there is some older literature on using exogenous testosterone as a method for male contraception.

Those data show testosterone enanthate (200 mg weekly) lowered sperm count to zero in 65-75% of men after 6 months (1,2). This decrease in fertility follows the decrease in the gonadotropic hormones, LH and FSH, via negative feedback due to the estradiol formed through aromatization of testosterone and subsequent binding to estrogen receptors in the hypothalamus and pituitary as well as the binding of testosterone to androgen receptors in the hypothalamus.

While the decrease in gonadotropins occurs fairly rapidly, the decrease in sperm production (spermatogenesis) is a fairly slow process. This is partially because it takes around 8 weeks for the sperm production process to be completed (3).

Despite not causing complete suppression of sperm production in all men, this 200 mg/weekly injection was around 98 to 99% effective at preventing pregnancy, making it on par with hormonally-based contraceptive methods in women.

Upon discontinuation of testosterone, at least at this dose, most will have a “normal” sperm count within 12 months without using medications to accelerate recovery. However, despite having a “normal” sperm count, around half of men may not reach their baseline levels of sperm production.

Of course, 200 mg/week of testosterone enanthate isn’t the same as what a heavy steroid user takes. Most individuals using AAS recover to a “normal” level of sperm production within 4-6 months post-use, although some may take up to 2-3 years, and some, albeit a minority, may never recover (4).

Juicing With Ancillary Medications

One study found that in a group of mainly bodybuilders, concomitant use of large doses of AAS with hCG during cycles lasting between approximately 1 to 9 months maintained sperm production, albeit with an increase in the number of morphologically abnormal sperm (5). I suspect adding FSH to the protocol would’ve helped reduce the number of abnormal sperm.

Interestingly, age and lifetime use of AAS were not associated with sperm concentrations, although there was a weak inverse correlation between daily AAS dose and sperm concentration.

Another study followed men taking large doses of testosterone and other steroids along with ancillary medications, including estrogen antagonists and aromatase inhibitors used at a rate of around 90% (55% were also using hCG post-cycle). Nearly 91% of those users were able to conceive (6). This is pretty impressive.

Interestingly, there were no differences in duration to conception, difficulty of achieving pregnancy, or need for medications/surgery when comparing those actively using during attempted conception versus those not. Those actively using testosterone and achieving pregnancy, confusingly, didn’t report using antiestrogens or PCT at a greater rate than those not actively using testosterone.

The notion that concomitant use of estrogen antagonists could support fertility during a cycle is at least partially supported by past studies administering clomiphene at fairly high doses (e.g., 100 mg one to two times daily). In these studies, clomiphene was not only able to prevent suppression of LH and FSH despite supraphysiological doses of exogenous testosterone (15 mg free base testosterone intravenously and 25 mg injection of testosterone propionate) but caused a surge of these hormones (7,8).

However, this approach is likely more successful with TRT versus AAS. High doses of various steroids may overcome the elevation of LH/FSH seen with SERM use, at least based on a less-controlled study (5).

In any event, these data support the notion that if LH can be maintained during cycles (or hCG is used), this alone may support ITT enough for sperm production.

One review paper actually made recommendations to those actively using AAS/TRT while attempting to conceive. It recommended hCG along with clomiphene as the first approach, followed by hCG and FSH (ditching the clomiphene) if a sufficient FSH response isn’t seen with 25 mg/day of clomiphene (9).

TRT Without Ancillary Medications

Ceasing TRT eventually allows most men to regain sperm production, although the timeframe is much longer (up to 2-3 years) without ancillary medications. Of course, some may never return to “normal” sperm production rates without ancillary therapy. However, since the point for most TRT patients is to stay on for the rest of their lives, there aren’t a lot of options. However, there could be therapeutic options that don’t cause as much suppression of LH/FSH.

The few available studies suggest that intramuscular testosterone injections are probably the most suppressive, followed by gels/patches. The least suppressive was an intranasal gel (Natesto) (10).

Another study found the likelihood of LH suppression with intramuscular testosterone versus transdermal was around 5.6 fold. The only route of administration that had a statistically significant association with LH suppression was intramuscular (2.4 times more likely) (11).

Finally, another study measured 17-hydroxyprogesterone as a surrogate for ITT and found intranasal testosterone produced less of a decrease as compared to testosterone pellets and intramuscular testosterone (12).

TRT With Ancillary Medications

Some data shows that an hCG dose of 500 I.U. every other day during TRT can preserve normal sperm production (13). Hypothetically, using a SERM such as clomiphene might produce similar results, considering past studies evaluating gonadotropin levels in response to supraphysiological doses of testosterone as well as results of a study administering tamoxifen and testosterone undecanoate in men with low sperm count (14).

In the review paper addressing fertility while actively using AAS, the authors treated TRT and AAS use similarly and recommended using hCG along with clomiphene if you want to make babies.

One variable that hasn’t been addressed is the morphology of sperm in those using hCG concomitantly with testosterone. It’s possible that this may require a source of FSH, whether endogenously produced via an anti-estrogen or supplemented via an exogenous source.

Regardless of the approach, it’s important to remember that some men, whether on TRT or AAS, may never fully recover baseline fertility. The data suggest younger men that haven’t been on TRT for very long have a rather high probability of fertility recovery for a given amount of time after ceasing TRT and using ancillary medications afterward (15). Conversely, older men that have been on longer have a lower probability.

It isn’t clear whether this is a reflection of the pattern of use or simply a reflection of the fact that those who truly need TRT earlier in life are already potentially suffering from infertility prior to any intervention. In any event, this applies to men who didn’t use any form of ancillary medications during their course of TRT. It’s currently unknown if that would prevent such occurrences in every case, although it’s reasonable to suspect that it would in most cases.

Take-Home Points

  • If you’re trying to conceive, consider abstaining from any AAS or TRT, if possible.
  • If abstaining isn’t possible, talk with a specialist about using hCG and either clomiphene or exogenous FSH while you’re using.
  • Making babies while juicing or using TRT is possible if ancillary medications are used.
  • However, making babies isn’t guaranteed. Some men may fail to achieve conception even after discontinuing TRT/AAS use and using ancillary medications to restore fertility or attempting to continue using TRT/AAS and using ancillary medications to preserve fertility.
  • Use of SERMs may prevent decreased ITT and decreased fertility when used with TRT, although more research is needed. This is less likely to work with high doses of varied steroids seen with typical cycles.
  • Age and length of use, at least when it comes to TRT without ancillary medication, are associated with a decreased probability of fertility restoration.
  • Age and length of use when it comes to AAS use are not associated with sperm production when using hCG during a cycle.

The natural T booster:

Biotest

References

References

  1. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril. 1996 Apr;65(4):821-9. Erratum in: Fertil Steril 1996 Jun;65(6):1267. PMID: 8654646.
  2. Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990 Oct 20;336(8721):955-9. PMID: 1977002.
  3. Thirumalai A, Page ST. Male Hormonal Contraception. Annu Rev Med. 2020 Jan 27;71:17-31. doi: 10.1146/annurev-med-042418-010947. Epub 2019 Sep 19. PMID: 31537185.
  4. Whitaker DL, Geyer-Kim G, Kim ED. Anabolic steroid misuse and male infertility: management and strategies to improve patient awareness. Expert Rev Endocrinol Metab. 2021 May;16(3):109-122. doi: 10.1080/17446651.2021.1921574. Epub 2021 May 11. PMID: 33973822.
  5. Karila T, Hovatta O, Seppälä T. Concomitant abuse of anabolic androgenic steroids and human chorionic gonadotrophin impairs spermatogenesis in power athletes. Int J Sports Med. 2004 May;25(4):257-63. doi: 10.1055/s-2004-819936. PMID: 15162244.
  6. Avant RA, Charchenko CM, Alom M, Westerman ME, Maldonado F, Miest T, Trost L. Medication patterns and fertility rates in a cohort of anabolic steroid users. Transl Androl Urol. 2018 May;7(Suppl 2):S198-S204. doi: 10.21037/tau.2018.05.05. PMID: 29928618; PMCID: PMC5989110.
  7. Winters SJ, Janick JJ, Loriaux DL, Sherins RJ. Studies on the role of sex steroids in the feedback control of gonadotropin concentrations in men. II. Use of the estrogen antagonist, clomiphene citrate. J Clin Endocrinol Metab. 1979 Feb;48(2):222-7. doi: 10.1210/jcem-48-2-222. PMID: 372203.
  8. Naftolin F, Judd HL, Yen SS. Pulsatile patterns of gonadotropins and testosterone in man: the effects of clomiphene, with and without testosterone added. J Clin Endocrinol Metab. 1973 Feb;36(2):285-8. doi: 10.1210/jcem-36-2-285. PMID: 4683184.
  9. Tatem AJ, Beilan J, Kovac JR, Lipshultz LI. Management of Anabolic Steroid-Induced Infertility: Novel Strategies for Fertility Maintenance and Recovery. World J Mens Health. 2020 Apr;38(2):141-150. doi: 10.5534/wjmh.190002. Epub 2019 Mar 26. PMID: 30929329; PMCID: PMC7076311.
  10. Masterson TA, Turner D, Vo D, Blachman-Braun R, Best JC, Westfield G, Bryson N, Ramasamy R. The Effect of Longer-Acting vs Shorter-Acting Testosterone Therapy on Follicle Stimulating Hormone and Luteinizing Hormone. Sex Med Rev. 2021 Jan;9(1):143-148. doi: 10.1016/j.sxmr.2020.07.006. Epub 2020 Sep 8. PMID: 32912767.
  11. Miranda EP, Schofield E, Matsushita K, Katz DJ, Nelson CJ, Benfante N, Mulhall JP. Luteinizing Hormone Suppression Profiles in Men Treated With Exogenous Testosterone. J Sex Med. 2022 Sep;19(9):1359-1365. doi: 10.1016/j.jsxm.2022.06.001. Epub 2022 Jul 14. PMID: 35842309.
  12. Diaz P, Reddy R, Blachman-Braun R, Zucker I, Dullea A, Gonzalez DC, Kresch E, Ramasamy R. Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials. World J Mens Health. 2023 Apr;41(2):390-395. doi: 10.5534/wjmh.210261. Epub 2022 Apr 22. PMID: 35791295; PMCID: PMC10042650.
  13. Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol. 2013 Feb;189(2):647-50. doi: 10.1016/j.juro.2012.09.043. Epub 2012 Dec 20. PMID: 23260550.
  14. Adamopoulos DA, Nicopoulou S, Kapolla N, Karamertzanis M, Andreou E. The combination of testosterone undecanoate with tamoxifen citrate enhances the effects of each agent given independently on seminal parameters in men with idiopathic oligozoospermia. Fertil Steril. 1997 Apr;67(4):756-62. doi: 10.1016/s0015-0282(97)81379-9. PMID: 9093207.
  15. Kohn TP, Louis MR, Pickett SM, Lindgren MC, Kohn JR, Pastuszak AW, Lipshultz LI. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril. 2017 Feb;107(2):351-357.e1. doi: 10.1016/j.fertnstert.2016.10.004. Epub 2016 Nov 14. PMID: 27855957; PMCID: PMC5292276.

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