This blog post is a continuation in a series on the recovery of men’s natural testosterone production and fertility after the use of anabolic and androgenic steroids.
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A REVIEW
Plainly, your brain’s hypothalamus is the key initiator of spermatogenesis. It sends a signal to your pituitary to produce the gonadotropins LH and FSH. LH and FSH increase intratesticular testosterone and promote the differentiation and maturation of sperm, respectively. When endogenous (or exogenous) testosterone is high, it prevents your hypothalamus from setting off the chain reaction that raises LH, thereby reducing intratesticular testosterone. When estrogen is high, it prevents your hypothalamus from raising LH as well as FSH.
When testosterone and estrogen are high, your body quits producing intratesticular testosterone and quits differentiating and maturing sperm in the testis.
The tools that have been used to repair HPG axis function are human chorionic gonadotropin (hCG), human menopausal gonadotropin (HMG), recombinant FSH (rFSH), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). This blog post will succinctly review the use of hCG, hMG, and rFSH.
LH AND FSH RECEPTOR ACTIVATION
Human chorionic gonadotropin (hCG) was originally derived of the urine of women, though recent recombinant versions appear equally effective[1]. It is structurally similar to both LH and FSH. The difference in its structure allow it a greater half-life than LH (36 hours as opposed to 30 minutes) and increased receptor activity at the LH receptor, making it a useful analogue of LH. Remember, LH’s main purpose is to increase intratesticular testosterone (ITT), which is what hCG does as well. As a result of the increased ITT, hCG can promote spermatogenesis.
Human menopausal gonadotropin (hMG) was originally derived from the urine of post-menopausal women. The majority of it consists of urinary proteins that have no use for enhancing fertility, though a minority of it contains FSH, LH, and hCG[2]. To enhance its use, highly purified forms of hMG have been made that contain a lesser quantity of undesirable urinary proteins. Moreover, the recent development of recombinant FSH (rFSH) has greatly improved upon the specificity of hMG at the FSH receptor. There has yet to be a comparison of hMG and rFSH for the purpose of improving spermatogenesis in men, but rFSH is already preferred because of the concern over the theoretical risk of developing Creutzfeld-Jakob disease from urinary hMG.
Essentially, in clinic hCG is used to simulate the effect of LH, while hMG (and rFSH) is used to simulate the effect of FSH. hCG increases intratesticular testosterone, producing spermatogenesis, while hMG and rFSH promote the differentiation and maturation of these sperm.
hCG, hMG, OR hCG + hMG?
hCG alone can restored fertility in 70% of patients, especially in those with testis over 4 cm in length, though further improvements are observed when hMG is included[3]. On the other hand, rFSH alone or in combination with TRT does not restore fertility, while rFSH in combination with hCG does[4]. A recent meta-analysis showed that recovery is superior when hCG is combined with rFSH[5].
PROTOCOLS FROM THE RESEARCH
My review of clinical studies indicates that the procedure favored by fertility doctors working with ex-AAS users is to begin with hCG as a monotherapy for 3-6 months. Doses range from 1,500-5,000 IU twice or thrice weekly, with the dose being titrated according to responses in serum testosterone levels. There is evidence of clinical success with a single weekly dose of 10,000 IU, but this is not the norm in clinical practice[6].
When enough spermatogenesis occurs, rFSH is administered at a dose of 75-400 IU twice or thrice weekly, titrating the dose according to results from semen. With this protocol, 44% of patients succeed in 6 months, though some require as many as 144 months to recover fertility[7].
Note that a lower dose of hCG therapy, at 500 IU thrice weekly, has been shown to maintain healthy semen characteristics across all parameters in those undergoing low-dose testosterone replacement therapy[8].
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[1] Trinchard-Lugan, I., Khan, A., Porchet, H. C., & Munafo, A. (2002). Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers. Reproductive biomedicine online, 4(2), 106-115. [2] Lehert, P., Schertz, J. C., & Ezcurra, D. (2010). Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis. Reproductive biology and endocrinology, 8(1), 112. [3] Vicari, E., Mongioi, A., Calogero, A. E., Moncada, M. L., Sidoti, G., Polosa, P., & D'AGATA, R. (1992). Therapy with human chorionic gonadotrophin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism‐long‐term follow‐up. International journal of andrology, 15(4), 320-329. [4] Schaison, G. I. L. B. E. R. T., Young, J. A. C. Q. U. E. S., Pholsena, M. A. R. Y. S. E., Nahoul, K. H. A. L. I. L., & Couzinet, B. E. A. T. R. I. C. E. (1993). Failure of combined follicle-stimulating hormone-testosterone administration to initiate and/or maintain spermatogenesis in men with hypogonadotropic hypogonadism. The Journal of Clinical Endocrinology & Metabolism, 77(6), 1545-1549. [5] Rastrelli, G., Corona, G., Mannucci, E., & Maggi, M. (2014). Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study. Andrology, 2(6), 794-808. [6] Menon, D. K. (2003). Successful treatment of anabolic steroid–induced azoospermia with human chorionic gonadotropin and human menopausal gonadotropin. Fertility and sterility, 79, 1659-1661. [7] Ishikawa, T., Ooba, T., Kondo, Y., Yamaguchi, K., & Fujisawa, M. (2007). Assessment of gonadotropin therapy in male hypogonadotropic hypogonadism. Fertility and sterility, 88(6), 1697-1699. [8] Hsieh, T. C., Pastuszak, A. W., Hwang, K., & Lipshultz, L. I. (2013). Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. The Journal of urology, 189(2), 647-650.
