Male Fertility: Can Testosterone be Optimized Without Testosterone Replacement Therapy?

IFM’s Advanced Practice Modules (APM) offer insight into a range of clinical conundrums and provide useful clinical pearls on approaching care through the functional medicine lens. Below is a question that is frequently asked by attendees during the program.

Testosterone replacement therapy is contraindicated in men seeking fertility as exogenous testosterone will impair spermatogenesis. Young men with low testosterone should have an etiology identified prior to treatment if possible (primary/secondary/combined and congenital vs acquired).1

Lifestyle factors that can be addressed to support healthy testosterone levels include maintaining a healthy body weight and addressing sources of chronic inflammation (including metabolic endotoxemia),2 reducing exposures to endocrine-disrupting chemicals3-6 and toxic metals,7 and limiting alcohol8 and cannabis9 intake.

Nutrient considerations include vitamin D10 and adequate zinc intake.11 Evidence also supports the use of Mucuna pruriens and Withania somnifera (ashwagandha) to improve testosterone concentrations and serum parameters. Despite inconclusive evidence for use of Tribulus terrestris as a testosterone booster, it may provide advantageous effects on sperm parameters in men with idiopathic infertility.12

In post-pubescent men desiring fertility, medication management is an option. Clomiphene citrate works as an SERM to block E2 negative feedback on hypothalamic receptors, functionally increasing LH/FSH.

If FSH and LH (hCG) levels are both optimal, sperm counts move into the normal range. hCG increases serum testosterone while increasing testicular volume and sperm count. The pro-fertility and testicular size effects of hCG are maximized when FSH is in the normal range. Start with hCG 1,500 IU subcutaneous injection for three weeks until testosterone levels induce spermatogenesis, followed by 150 IU rFSH s.c. three times per week to support and maintain the process. Pregnancy rates at 9-12 months reach 50-80%.13-15

Clinical takeaway: There are alternatives to testosterone replacement therapy for men desiring fertility. A comprehensive approach likely includes diet, lifestyle, botanical, and pharmaceutical intervention as needed.

Discover new ways to support male hormonal health at the upcoming Hormone Advanced Practice Module. Clinicians will learn to created personalized treatments using nutrition, supplementation, and other lifestyle considerations.



  1. Ramasamy R, Armstrong JM, Lipshultz LI. Preserving fertility in the hypogonadal patient: an update. Asian J Androl. 2015;17(2):197-200. doi:10.4103/1008-682x.142772
  2. Tremellen K. Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) – a novel theory for the development of late onset hypogonadism in obese men. Basic Clin Androl. 2016;26:7. doi:10.1186/s12610-016-0034-7
  3. Johnson PI, Stapleton HM, Mukherjee B, Hauser R, Meeker JD. Associations between brominated flame retardants in house dust and hormone levels in men. Sci Total Environ. 2013;445-446:177-184. doi:10.1016/j.scitotenv.2012.12.017
  4. Specht IO, Toft G, Hougaard KS, et al. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men. Environ Int. 2014;66:146-156. doi:10.1016/j.envint.2014.02.002
  5. Joensen UN, Veyrand B, Antignac JP, et al. PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men [published correction appears in Hum Reprod. 2014;29(7):1600]. Hum Reprod. 2013;28(3):599-608. doi:10.1093/humrep/des425
  6. Meeker JD, Calafat AM, Hauser R. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl. 2009;30(3):287-297. doi:10.2164/jandrol.108.006403
  7. Wirth JJ, Mijal RS. Adverse effects of low level heavy metal exposure on male reproductive function. Syst Biol Reprod Med. 2010;56(2):147-167. doi:10.3109/19396360903582216
  8. Jensen TK, Gottschau M, Madsen JO, et al. Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open. 2014;4(9):e005462. doi:10.1136/bmjopen-2014-005462
  9. du Plessis SS, Agarwal A, Syriac A. Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility. J Assist Reprod Genet. 2015;32(11):1575-1588. doi:10.1007/s10815-015-0553-8
  10.  Pilz S, Frisch S, Koertke H, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metabol Res. 2011;43(3):223-225. doi:10.1055/s-0030-1269854
  11.  Netter A, Hartoma R, Nahoul K. Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Arch Androl. 1981;7(1):69-73. doi:10.3109/01485018109009378
  12.  Santos HO, Howell S, Teixeira FJ. Beyond tribulus (Tribulus terrestris L.): the effects of phototherapies on testosterone, sperm and prostate parameters. J Ethnopharmacol. 2019;235:392-405. doi:10.1016/j.jep.2019.02.033
  13.  Schaison G, Young J, Pholsena M, Nahoul K, Couzinet B. Failure of combined follicle-stimulating hormone-testosterone administration to initiate and/or maintain spermatogenesis in men with hypogonadotropic hypogonadism [published correction appears in J Clin Endocrinol Metab. 1994;78(4):846]. J Clin Endocrinol Metab. 1993;77(6):1545-1549. doi:10.1210/jcem.77.6.8263139
  14.  Rajkanna J, Tariq S, Oyibo SO. Successful fertility treatment with gonadotrophin therapy for male hypogonadotrophic hypogonadism. Endocrinol Diabetes Metab Case Rep. 2016;2016:150124. doi:10.1530/EDM-15-0124
  15.  Rey RA, Grinspon RP, Gottlieb S, et al. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach. Andrology. 2013;1(1):3-16. doi:10.1111/j.2047- 2927.2012.00008.x