Clinical trial NCT02268032: Assess the Effect of Dehydroepiandrosterone (DHEA) or Other Androgenic Agents Over Markers of Ovarian Reserve
Official title: Assess the Effect of DHEA or Other Androgenic Agents on Ovarian Reserve Markers in Women With Diminished Ovarian Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Women
Infertility, Female
Keywords: Hormone replacement therapy
Lead sponsor: Laboratorios Andromaco S.A.
Sponsor class: INDUSTRY
First posted: 2014-10-20
Enrollment: 94
Sex: FEMALE
Minimum age (years): 38
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study was conducted to evaluate the effect of a continuous administration of dehydroepiandrosterone (DHEA) or other androgenic agents on ovarian reserve markers in women with diminished ovarian reserve (ROD), such as antral follicle count (AFC) and anti-Müllerian hormone (AMH) concentrations.

Detailed description: Healthy women attending the clinic of the Mother and Health Research Institute (IDIMI) were invited to participate, if they could not become pregnant due to surgical sterilization, and if they presented no contraindications to use androgen therapy.

Project Objectives :

The general objective was to evaluate pharmacokinetic parameters of three vaginal rings containing DHEA, testosterone, or combination of both hormones in women.

Secondary objectives were to assess effects on the hormonal profile, tolerability and incidence of adverse events.

* DHEA and/or, testosterone levels
* Estradiol, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), androstenedione, morning cortisol, insulin growth factor 1 (IGF-1) levels
* Tolerability and safety assessment by the use of the vaginal ring.
* The incidence of adverse events

Eligibility criteria: Inclusion Criteria:

1. Women between 38 and 45 years of age who have not used hormonal contraceptive methods at least for the past two months, or who have been surgically sterilized, with no contraindications for androgenic therapy.
2. Women with preserved menstrual cycles.
3. Women smoking less than 5 cigarettes daily.
4. Anti-Müllerian hormone (AMH) between 0.5-1.1 ng/mL
5. Total antral follicle count (AFC) 5-7

Exclusion Criteria:

1. Women receiving medications that interact with DHEA metabolism (Anastrozole, exemestane, Fulvestrant, Insulin, Letrozole, Tamoxifen, Triazolam).
2. Women with diabetes mellitus
3. Women with untreated or decompensated endocrine disorders
4. Women with a prior history of ovarian surgery or oophorectomy

Primary outcomes:
measure: Effect of the association of DHEA plus testosterone over ovarian reserve markers
timeFrame: Before therapy start and up to 2 months thereafter
Secondary outcomes:
measure: Plasma levels of sex hormone binding globulin (SHBG), androstenedione, morning cortisol, insulin growth factor 1 (IGF-1), testosterone, dehydroepiandrosterone, follicle stimulating hormone (FSH), and estradiol
timeFrame: Before therapy start and up to 2 months thereafter
measure: Tolerability of using the vaginal ring
timeFrame: After therapy start (vaginal ring insertion) and after 2 months (ring extraction)
measure: Number of subjects with adverse events per treatment group
timeFrame: From therapy start to up to 2 months
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Mother and Health Research Institute (IDIMI), Faculty of Medicine, University of Chile
state: International
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References:
citation: Alexander JL, Kotz K, Dennerstein L, Kutner SJ, Wallen K, Notelovitz M. The effects of postmenopausal hormone therapies on female sexual functioning: a review of double-blind, randomized controlled trials. Menopause. 2004 Nov-Dec;11(6 Pt 2):749-65. doi: 10.1097/01.gme.0000142887.31811.97.
citation: Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod. 2006 Nov;21(11):2845-9. doi: 10.1093/humrep/del254. Epub 2006 Sep 22.
citation: Balasch J, Fabregues F, Penarrubia J, Carmona F, Casamitjana R, Creus M, Manau D, Casals G, Vanrell JA. Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poor-responder IVF patients with normal basal concentrations of FSH. Hum Reprod. 2006 Jul;21(7):1884-93. doi: 10.1093/humrep/del052. Epub 2006 Mar 3.
citation: Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev. 2009 Aug;30(5):465-93. doi: 10.1210/er.2009-0006. Epub 2009 Jul 9.
citation: Fabregues F, Penarrubia J, Creus M, Manau D, Casals G, Carmona F, Balasch J. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod. 2009 Feb;24(2):349-59. doi: 10.1093/humrep/den428. Epub 2008 Dec 3.
citation: Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
citation: Gleicher N, Weghofer A, Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online. 2010 Sep;21(3):360-5. doi: 10.1016/j.rbmo.2010.04.006. Epub 2010 Apr 18.
citation: Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S. Interventions for 'poor responders' to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010 Jan 20;(1):CD004379. doi: 10.1002/14651858.CD004379.pub3.
citation: Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman A. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod. 2010 Oct;25(10):2496-500. doi: 10.1093/humrep/deq220. Epub 2010 Aug 21.