Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series

Abstract

In patients with poor response to ovarian stimulation with gonadotrophins, growth hormone (GH) is sometimes used to increase paracrine insulin-like growth factor-1 (IGF-1) effect. We postulated that dehydroepiandrosterone (DHEA) administration to poor responders would augment gonado-trophin effect via a similar mechanism. Baseline ovarian stimulation response to a cycle with DHEA in five healthy non-smoking women <41 years old was compared with day 3 FSH <20 mIU/ml. All had documented poor response to vigorous gonadotrophin administration. After day 2 ultrasounds, DHEA-sulphate (DHEA-S), FSH, human chorionic gonadotrophin (HCG), and testosterone were measured, and the women were given 80 mg/day of oral micronized DHEA for 2 months. While still on DHEA, they underwent ovarian stimulation with FSH given i.m. twice a day, and HCG (10 000 IU) at follicular maturity, followed by intrauterine insemination. Cycle parameters assessed were peak oestradiol, and peak oestradiol/ampoule. The DHEA/ovarian stimulation cycles occurred between 4 and 24 months after the control cycles. After 2 months DHEA treatment, DHEA-S increased to 544 +/- 55 microg/dl, and testosterone increased to 67.3 +/- 6.1 ng/dl. All five subjects (six cycles; one subject had two DHEA cycles) had increased responsiveness; peak oestradiol concentrations increased from 266.3 +/- 69.4 pg/ml to 939.8 +/- 418.9 pg/ml. The oestradiol/ampoule ratio increased in all six cycles, by a mean of 2.94 +/- 0.50 fold (P = 0.012). One of the cycles resulted in a delivered twin pregnancy. In this small series, DHEA improved response to ovarian stimulation even after controlling for gonadotrophin dose. Supplemental DHEA treatment during ovarian stimulation may represent a novel way to maximize ovarian response.

Is there a role for DHEA supplementation in women with diminished ovarian reserve?

“…Casson et al were the first to describe the therapeutic benefits of DHEA supplementation in women with diminished ovarian reserve [15]. They described five subjects, all of who were below 41 of age with normal FSH concentrations who had poor response to ovarian stimulation with gonadotropins in ovulation induction followed by intra uterine insemination cycles.…”

“…They described five subjects, all of who were below 41 of age with normal FSH concentrations who had poor response to ovarian stimulation with gonadotropins in ovulation induction followed by intra uterine insemination cycles. After oral supplementation with 80 mg of micronized DHEA for two months, their peak estradiol level tripled and their response to stimulation increased by two folds and concluded that DHEA supplementation might be a novel way to maximize ovarian response in poor responders [15]. The mechanism by which DHEA exerts its effects is uncertain; however, the authors speculated it may have a role in increasing the serum concentrations of IGF-1, which in turn may improve the response to gonadotropins [15].…”

“…After oral supplementation with 80 mg of micronized DHEA for two months, their peak estradiol level tripled and their response to stimulation increased by two folds and concluded that DHEA supplementation might be a novel way to maximize ovarian response in poor responders [15]. The mechanism by which DHEA exerts its effects is uncertain; however, the authors speculated it may have a role in increasing the serum concentrations of IGF-1, which in turn may improve the response to gonadotropins [15]. Previously, Casson et al studied the effect of DHEA supplementation on IGF-1 and High Density lipoprotein in postmenopausal women [16].…”

“…Hodges et al suggested that changes in oocytes growth would influence meiotic chromosome segregation [32]. DHEA supplementation results in an increased ovarian IGF-1 expression, which is reduced in poor responders [15]. The role of androgens in follicular development was described in multiple studies [33][34][35][36][37].…”

“…There is no consensus on the optimal or the maximal dose of DHEA, nor the duration of use, though most studies did not exceed 6 months, and to our knowledge, no published data has evaluated the plasma levels of DHEA after supplementation at various time intervals in women with diminished Table 2 Potential mechanisms of action of DHEA in infertile women Potential mechanisms of DHEA action 1-Improves steroidogenesis as a precursor for estradiol and testosterone 2-Influences ovarian follicular growth by acting as a ligand for androgen receptors 3-Increases IGF-1 4-Creation of PCOS-like characteristics and increasing LH 5-Acts as the pre-hormone for follicular fluid testosterone 6-Reduces age-related aneuploidy by affecting meiotic chromosome segregation 7-Increases small antral follicles and AMH levels [15]. The side effects of such low dosage are minimal and related to its androgenic effects, which include hair loss, oily skin, and acne vulgaris.…”