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Testosterone Cypionate Fertility Suppression: Supplements With the Best Evidence

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At a glance

  • Supplement trials / enrolled infertile men, not men using testosterone [3][4]
  • hCG 500 IU every other day / intratesticular testosterone 26% above baseline in that dose group of a 29-man randomized study [2]
  • hCG-based combination therapy / spermatogenesis returned or improved in 47 of 49 men [5]
  • Recovery at 12 months / 46 of 66 men reached a total motile count above 5 million [6]
  • Endocrine Society / recommends against testosterone in men planning near-term fertility [7]

Do any supplements preserve fertility on testosterone cypionate?

The supplement trials below enrolled infertile men, not men using testosterone.

CoQ10 has the largest trial: 212 men with idiopathic oligoasthenoteratospermia, 106 taking 300 mg daily for 26 weeks, improved sperm density and motility versus placebo [3]. A meta-analysis of three trials found higher sperm concentration and motility but no increase in pregnancy rates [8]. A meta-analysis of 20 studies found lower seminal zinc in infertile men, and zinc supplementation increased semen volume, motility and normal morphology [4]. In a 468-man trial, selenium 200 mcg daily, alone or with 600 mg N-acetyl-cysteine, improved all semen parameters over 26 weeks [9]. In a 46-man randomized pilot in oligospermic men, sperm count rose from 9.59 to 25.61 million/mL in the 21 men taking ashwagandha 675 mg daily for 90 days, with minimal improvement in the 25 men given placebo [10].

What has been studied during testosterone use?

hCG mimics LH and stimulates Leydig cells directly. In a randomized study of 29 men on 200 mg testosterone enanthate weekly, intratesticular testosterone fell 94% with placebo, from 1,234 to 72 nmol/L; hCG every other day raised it dose-dependently, with 500 IU leaving it 26% above baseline after 3 weeks [2]. The study measured testicular fluid testosterone, not sperm or pregnancies.

Two retrospective series reported sperm recovery with hCG-based combination treatment. In 49 men with azoospermia or severe oligospermia on testosterone, hCG 3,000 units every other day plus clomiphene, tamoxifen, anastrozole or recombinant FSH returned or improved spermatogenesis in 47 (95.9%), average 4.6 months [5]. In 66 men, high-dose hCG plus a SERM after stopping testosterone brought 46 (70%) to a total motile count above 5 million within 12 months [6].

Enclomiphene has also been studied as an alternative to testosterone: in two trials, it maintained sperm concentration while testosterone gel did not [11].

The Depo-Testosterone label lists oligospermia at high dosages [1]. The Endocrine Society recommends against starting testosterone therapy in men planning fertility in the near term [7].

Frequently asked questions

Can any supplement prevent fertility suppression on testosterone cypionate?
No supplement has been shown to. In men on testosterone enanthate, prescription hCG maintained intratesticular testosterone [2].
Which supplement has the most sperm data?
CoQ10: in 212 infertile men, 106 taking 300 mg daily improved sperm density and motility versus placebo [3]. A meta-analysis found higher concentration and motility but no increase in pregnancy rates [8].
Does hCG preserve fertility on testosterone cypionate?
In a 29-man randomized study of weekly testosterone enanthate, the group given hCG 500 IU every other day had intratesticular testosterone 26% above baseline, but the study did not measure sperm or pregnancies [2]. Two retrospective series reported sperm recovery with hCG-based combination treatment [5][6].
Does ashwagandha improve sperm count?
In a 46-man randomized pilot in oligospermic men, sperm count rose from 9.59 to 25.61 million/mL in the 21 men taking 675 mg daily for 90 days, with minimal improvement in the placebo group [10].

References

  1. U.S. National Library of Medicine, DailyMed. Depo-Testosterone (cypionate) intramuscular, Pharmacia & Upjohn/Pfizer (testosterone cypionate) prescribing information. Depo-Testosterone (cypionate) intramuscular, Pharmacia & Upjohn/Pfizer (testosterone cypionate) label
  2. Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, et al. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. 2005;90(5):2595-602. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression
  3. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009;182(1):237-48. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men
  4. Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, et al. Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis. Sci Rep. 2016;6:22386. Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis
  5. Wenker EP, Dupree JM, Langille GM, Kovac J, Ramasamy R, Lamb D, et al. The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use. J Sex Med. 2015;12(6):1334-7. The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use
  6. Kohn TP, Louis MR, Pickett SM, Lindgren MC, Kohn JR, Pastuszak AW, et al. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril. 2017;107(2):351-357.e1. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy
  7. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline
  8. Lafuente R, González-Comadrán M, Solà I, López G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis. J Assist Reprod Genet. 2013;30(9):1147-56. Coenzyme Q10 and male infertility: a meta-analysis
  9. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009;181(2):741-51. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study
  10. Ambiye VR, Langade D, Dongre S, Aptikar P, Kulkarni M, Dongre A. Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. Evid Based Complement Alternat Med. 2013;2013:571420. Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study
  11. Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. 2016;117(4):677-85. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement
Evidence overview for Testosterone Cypionate Fertility Suppression: Supplements With the Best Evidence