Skip to main content
SpringerLink
Log in

Clinical Assisted Reproduction: Altered Balance Between the 5α-Reductase and Aromatase Pathways of Androgen Metabolism During Controlled Ovarian Hyperstimulation with Human Menopausal Gonadotropins

  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose: To evaluate androgen production and metabolism during controlled ovarian hyperstimulation.

Methods: Five women, aged 33–42, were studied. All participants were undergoing controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonist and human menopausal gonadotropins. Serum estradiol, estrone, androstenedione, testosterone, 3α-androstanediol glucuronide, and sex hormone-binding globulin levels were measured at 6 time points during the cycle.

Results: The levels of all steroids increased significantly from baseline during controlled ovarian hyperstimulation. Mean total testosterone levels increased from 0.29 ± 0.05 ng/mL to 0.58 ± 0.07 ng/mL after gonadotropin stimulation. Sex hormone-binding gonadotropin levels increased from 50 ± 16 nM to 73 ± 12 nM after gonadotropin stimulation. Estrone/androstenedione and estradiol/testosterone ratios, reflecting the aromatase pathway, increased whereas 3α-androstanediol glucuronide/androstenedione and 3α-androstanediol glucuronide/testosterone ratios, reflecting 5α-reductase activity, decreased.

Conclusions: Controlled ovarian hyperstimulation with human menopausal gonadotropins results in increased serum testosterone and androstenedione levels. Whereas there is an enhancement in androgen metabolism by aromatase, 5α-reductase activity with regard to androgen metabolism is diminished.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Martin KA, Hornstein MD, Taylor AE, Hall JE, Barbieri RL: Exogenous gonadotropin stimulation is associated with increases in serum androgen levels in in-vitro fertilization-embryo transfer cycles. Fertil Steril 1997;68:1011-1016

    Google Scholar 

  2. Adashi EY:The climacteric ovary as a functional gonadotropindriven androgen-producing gland. Fertil Steril 1994;62: 20-27

    Google Scholar 

  3. Gelety TJ, Surrey ES: Incomplete androgen and progesterone suppression following midluteal GnRHa prior to controlled ovarian hyperstimulation for IVF-ET. J Assist Reprod Genet 1997;14:525-530

    Google Scholar 

  4. Fanchin R, Righini C, Olivennes F, Taieb J, de Ziegler D, Frydman R: Premature plasma progesterone and androgen elevation are not prevented by adrenal suppression in in vitro fertilization. Fertil Steril 1997;67:115-119

    Google Scholar 

  5. Yong EL, Hillier SG, Turner M, Baird DT, Ng SC, Bongso A, Ratnam SS: Differential regulation of cholesterol side-chain cleavage (P450scc) and aromatase (P450arom) enzymemRNA expression by gonadotrophins and cyclic AMP in human granulosa cells. J Mol Endocrinol 1994;12:239-249

    Google Scholar 

  6. Polan ML, Daniele A, Russell JB, DeCherney AH: Ovulation induction with human menopausal gonadotropin compared to human urinary follicle-stimulating hormone results in a significant shift in follicular fluid androgen levels without discernible differences in granulosa-luteal cell function. J Clin Endocrinol Metab 1986;63:1284-1291

    Google Scholar 

  7. Steinkampf MP, Mendelson CR, Simpson ER: Regulation by follicle-stimulating hormone of the synthesis of aromatase cytochrome P-450 in human granulosa cells. Mol Endocrinol 1987;1:465-471

    Google Scholar 

  8. Yong EL, Baird DT, Yates R, Reichert LE Jr, Hillier SG: Hormonal regulation of the growth and steroidogenic function of human granulosa cells. J Clin Endocrinol Metab 1992;74:842-849

    Google Scholar 

  9. Paulson RJ, Serafini PC, Catalino JA, Lobo RA: Measurements of 3?,17ß-androstanediol glucuronide in serum and urine and the correlation with skin 5?-reductase activity. Fertil Steril 1986;46:222-226

    Google Scholar 

  10. Goebelsmann U, Horton R, Mestman JH, Arce JJ, Nagata Y, Nakamura RM, Thorneycroft IH, Mishell DR Jr: Male pseudohermaphroditism due to testicular 17ß-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 1973;36:867-879

    Google Scholar 

  11. Goebelsmann U, Arce JJ, Thorneycorft IH, Mishell DR Jr: Serum testosterone concentrations in women throughout the menstrual cycle and following hCG administration. Am J Obstet Gynecol 1974;119:445-452

    Google Scholar 

  12. Wong IL, Morris RS, Chang L, Spahn M-A, Stanczyk FZ, Lobo RA: A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995;80:233-238

    Google Scholar 

  13. Goebelsmann U, Bernstein GS, Gale JA, Kletzky OA, Nakamura RM, Coulson AM, Korelitz JJ: Serum gonadotropin, testosterone, estradiol and estrone levels prior to and following bilateral vasectomy. InVasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, JH Lepow, R Crozier (eds.), NewYork, Academic Press, 1979, pp. 165-175

    Google Scholar 

  14. Stanczyk FZ: Steroid hormones. In Mishell's Textbook of Infertility, Contraception, and Reproductive Endocrinology, 4th edn., RA Lobo, DR Mishell Jr, RJ Paulson, D Shoupe (eds.), Malden, Blackwell Science, 1997, pp. 46-66

    Google Scholar 

  15. Liu CH, Laughlin GA, Fischer UG, Yen SS: Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: Evidence for a reduced 17,20-desmolase enzymatic activity. J Clin Endocrinol Metab 1990;71:900-906

    Google Scholar 

  16. Medina M, Herrera J, Flores M, Martin O, Bermudez JA, Zarate A: Normal ovarian function in a mild form of late-onset 3ß-hydroxysteroid dehydrogenase deficiency. Fertil Steril 1986;46:1021-1025

    Google Scholar 

  17. Chang YT, Zhang L, Alkaddour HS, Mason JI, Lin K, Yang X, et al.: Absence of molecular defect in the type II 3ß-hydroxysteroid dehydrogenase (3ß-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3ß-HSD activity. Pediatr Res 1995;37:820-824

    Google Scholar 

  18. Speroff L, Glass RH, Kase NG, eds.: Hormone biosynthesis, metabolism, and mechanism of action. In Clinical Gynecologic Endocrinology and Infertility, 6th edn., Philadelphia, Lippincott Williams &Wilkins, 1999, pp. 31-105

  19. Holt JA: Reproductive hormones and their mechanisms of action. In Mishell's Textbook of Infertility, Contraception, and Reproductive Endocrinology, 4th edn., RA Lobo, DR Mishell Jr, RJ Paulson, D Shoupe (eds.), Malden, Blackwell Science, 1997, pp. 26-45

    Google Scholar 

  20. Toscano V, Balducci R, Bianchi P, Guglielmi R, Mangiantini A, Sciarra F: Steroidal and non-steroidal factors in plasma sex hormone binding globulin regulation. J Steroid Biochem Mol Biol 1992;43:431-437

    Google Scholar 

  21. Cassidenti DL, Paulson RJ, Serafini P, Stanczyk FZ, Lobo RA: Effects of sex steroids on skin 5?-reductase activity in vitro. Obstet Gynecol 1991;78:103-107

    Google Scholar 

  22. Krieg M, Schlenker A, Voigt K: Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol. Prostate 1985;6:233-240

    Google Scholar 

  23. Serafini PC, Catalino J, Lobo RA: The effect of spironolactone on genital skin 5?-reductase activity. J Steroid Biochem 1985;23:191-194

    Google Scholar 

  24. Serafini P, Lobo RA: Prolactin modulates peripheral androgen metabolism. Fertil Steril 1986;45:41-46

    Google Scholar 

  25. Kuttenn F, Rigaud C, Wright F, Mauvais-Jarvis P: Treatment of hirsutism by oral cyproterone acetate and percutaneous estradiol. J Clin Endocrinol Metab 1980;51:1107-1111

    Google Scholar 

  26. Dean HJ, Winter JS: The effect of five synthetic progestational compounds on 5?-reductase activity in genital skin fibroblast monolayers. Steroids 1984;43:13-24

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, California

    Cristin C. Slater, Lilly Chang, Frank Z. Stanczyk & Richard J. Paulson

Authors
  1. Cristin C. Slater
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilly Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Z. Stanczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard J. Paulson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slater, C.C., Chang, L., Stanczyk, F.Z. et al. Clinical Assisted Reproduction: Altered Balance Between the 5α-Reductase and Aromatase Pathways of Androgen Metabolism During Controlled Ovarian Hyperstimulation with Human Menopausal Gonadotropins. J Assist Reprod Genet 18, 527–533 (2001). https://doi.org/10.1023/A:1011914218410

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011914218410

Search

Navigation