Journal of Assisted Reproduction and Genetics

, Volume 24, Issue 12, pp 629–634 | Cite as

Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function

Symposium of the Aging Ovary

Abstract

Objective

We assessed the role of DHEA supplementation on pregnancy rates in women with diminished ovarian function.

Design

This is a case control study of 190 women with diminished ovarian function. The study group includes 89 patients who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4 months prior to entry into in vitro fertilization (IVF). The control group is composed of 101 couples who received infertility treatment, but did not use DHEA. The primary outcome was clinical pregnancy after the patient’s initial visit. We developed a Cox proportional hazards model to compare the proportional hazards of pregnancy among women using DHEA with the controls group.

Results

Cumulative clinical pregnancy rates were significantly higher in the study group (25 pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in study group (HR 3.8; 95% CI 1.2–11.8; p < 0.05).

Conclusions

DHEA treatment resulted in significantly higher cumulative pregnancy rates. These data support a beneficial effect of DHEA supplementation among women with diminished ovarian function.

Keywords

Dehydroepiandrosterone Diminished ovarian reserve Infertility In vitro fertilization, Pregnancy rates Age Life table analysis 

References

  1. 1.
    Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000;15(10):2129–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Barad D, Gleicher N. Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005;84(3):756.PubMedCrossRefGoogle Scholar
  3. 3.
    Barad, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006;21(11):2845–9.PubMedCrossRefGoogle Scholar
  4. 4.
    ASRM/SART-Registry. Assisted reproductive technology in the United States: 2000 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2004;81(5):1207–20.CrossRefGoogle Scholar
  5. 5.
    Barad D, Weghofer A, Gleicher N. O-291: evidence for an empiric definition of diminished ovarian reserve (DOR), ovarian resistance to stimulation and diagnosis of premature ovarian aging (POA), based on age-specific baseline FSH levels. Fertil Steril 2006;86(3, Supplement 1):S125–S6.CrossRefGoogle Scholar
  6. 6.
    Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol. Fertil Steril 1997;67(1):93–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Gleicher N, VanderLaan B, Pratt D, Karande V. Background pregnancy rates in an infertile population. Hum Reprod 1996;11(5):1011–2.PubMedGoogle Scholar
  8. 8.
    Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment-independent pregnancy among infertile couples. N Engl J Med 1983;309(20):1201–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Karande V, Gleicher N. A rational approach to the management of low responders in in-vitro fertilization. Hum Reprod 1999;14(7):1744–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Harper AJ, Buster JE, Casson PR. Changes in adrenocortical function with aging and therapeutic implications. Semin Reprod Endocrinol 1999;17(4):327–38.PubMedCrossRefGoogle Scholar
  11. 11.
    Hillier SG, Whitelaw PF, Smyth CD. Follicular oestrogen synthesis: The ‘two-cell, two-gonadotrophin’ model revisited. Mol Cell Endocrinol 1994;100(1–2):51–4.PubMedGoogle Scholar
  12. 12.
    Dorrington JH, Moon YS, Armstrong DT. Estradiol 17[beta] biosynthesis in cultured granulosa cells from hypophysectomized immature rats; stimulation by follicle stimulating hormone. Endocrinology 1975;97(5):1328–31.PubMedGoogle Scholar
  13. 13.
    Haning R Jr, Hackett R, Flood C, Loughlin J, Zhao Q, Longcope C. Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins. J Clin Endocrinol Metab 1993;76(5):1301–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Hillier SG. Sex steroid metabolism and follicular development in the ovary. Oxf Rev Reprod Biol 1985;7:168–222.PubMedGoogle Scholar
  15. 15.
    Daniel SAJ, Armstrong DT. Androgens in the ovarian microenvironment. Sem Reprod Endocrinol 1986;4(2):89–100.CrossRefGoogle Scholar
  16. 16.
    Gore-Langton R, Armstrong D. Follicular steroidogenesis and its control. In: Knobil E, Neill J, editors. The physiology of reproduction. New York: Raven Press; 1988. p. p. 331–85.Google Scholar
  17. 17.
    Harlow CR, Hillier SG, Hodges JK. Androgen modulation of follicle-stimulation hormone-induced granulosa cell steroidogenesis in the primate ovary. Endocrinology 1986;119(3):1403–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Vendola K, Zhou J, Wang J, Famuyiwa OA, Bievre M, Bondy CA. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Biol Reprod 1999;61(2):353–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Yan Z, Lee GY, Anderson E. Influence of dehydroepiandrosterone on the expression of insulin-like growth factor-1 during cystogenesis in polycystic rat ovaries and in cultured rat granulosa cells. Biol Reprod 1997;57(6):1509–16.PubMedCrossRefGoogle Scholar
  20. 20.
    Casson PR, Santoro N, Elkind-Hirsch K, et al. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial. Fertil Steril 1998;70(1):107–10.PubMedCrossRefGoogle Scholar
  21. 21.
    Frattarelli JL, Peterson EH. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril 2004;81(6):1713–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Barbieri RL, Sluss PM, Powers RD, et al. Association of body mass index, age, and cigarette smoking with serum testosterone levels in cycling women undergoing in vitro fertilization. Fertil Steril 2005;83(2):302–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Goswami SK, Das T, Chattopadhyay R, et al. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod 2004;19(9):2031–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Mitwally MF, Casper RF. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 2002;77(4):776–80.PubMedCrossRefGoogle Scholar
  25. 25.
    MacDougall M, Tan S, Balen A, Jacobs H. A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization. Hum Reprod 1993;8(2):233–7.PubMedGoogle Scholar
  26. 26.
    Maciel GAR, Baracat EC, Benda JA, et al. Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004;89(11):5321–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Amirikia H, Savoy-Moore RT, Sundareson AS, Moghissi KS. The effects of long-term androgen treatment on the ovary. Fertil Steril 1986;45(2):202–8.PubMedGoogle Scholar
  28. 28.
    Pache TD, Chadha S, Gooren LJ, et al. Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model or the study of polycystic ovarian syndrome? Histopathology.1991;19(5):445–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Kaipia A, Hsueh AJ. Regulation of ovarian follicle atresia. Annu Rev Physiol 1997;59:349–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Billig H, Furuta I, Hsueh AJ. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology 1993;133(5):2204–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Kroboth PD, Salek FS, Pittenger AL, Fabian TJ, Frye RF. DHEA and DHEA-S: a review. J Clin Pharmacol 1999;39(4):327–48.PubMedCrossRefGoogle Scholar
  32. 32.
    Kaaks R, Berrino F, Key T, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2005;97(10):755–65.PubMedCrossRefGoogle Scholar
  33. 33.
    McClamrock HD, Adashi EY. Gestational hyperandrogenism. Fertil Steril 1992;57(2):257–74.PubMedGoogle Scholar
  34. 34.
    Sir-Petermann T, Maliqueo M, Angel B, Lara HE, Perez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 2002;17(10):2573–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • David Barad
    • 1
    • 2
    • 5
    • 6
  • Hyama Brill
    • 3
    • 5
    • 6
  • Norbert Gleicher
    • 4
    • 5
    • 6
  1. 1.Department of Epidemiology and Social MedicineAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of Obstetrics and Gynecology & Women’s HealthAlbert Einstein College of MedicineBronxUSA
  3. 3.Department of Obstetrics and GynecologyLenox Hill HospitalManhattanUSA
  4. 4.Department of Obstetric and GynecologyYale University School of MedicineNew HavenUSA
  5. 5.The Center for Human Reproduction (CHR)New YorkUSA
  6. 6.The Foundation for Reproductive MedicineChicagoUSA

Personalised recommendations