Assess the Effect of Dehydroepiandrosterone (DHEA) or Other Androgenic Agents Over Markers of Ovarian Reserve

NCT02268032 | Completed Phase 1

• 1 other identifier: DVR+T001
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Women; Infertility, Female

Keywords

Hormone replacement therapy

Outcome Measures

Primary Outcomes (1)

• Effect of the association of DHEA plus testosterone over ovarian reserve markers

  The ovarian reserve markers antral follicle count (AFC) and anti-Müllerian hormone (AMH) were determined before and after hormonal therapy to compare the levels of both hormones between mono- and combination therapy and to investigate a potentially synergistic effect of the association of DHEA plus testosterone.

  Before therapy start and up to 2 months thereafter

Secondary Outcomes (3)

• 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

  Before therapy start and up to 2 months thereafter

• Tolerability of using the vaginal ring

  After therapy start (vaginal ring insertion) and after 2 months (ring extraction)

• Number of subjects with adverse events per treatment group

  From therapy start to up to 2 months

Study Arms (3)

Vaginal ring 1 (VRD)

EXPERIMENTAL

20 women using DHEA (VRD) for 2 menstrual cycles

Drug: DHEA

Vaginal ring 2 (VRaA)

EXPERIMENTAL

20 women using another androgenic agent (VRaA) for 2 menstrual cycles

Drug: Another Androgenic Agent (VRaA)

Vaginal ring 3 (VR2A)

EXPERIMENTAL

20 women using fixed combination of 2 androgenic agents (VR2A) for 2 menstrual cycles

Drug: Fixed combination of 2 androgenic agents (VR2A)

Interventions

DHEA DRUG

DHEA 2.2 g in vaginal ring

Vaginal ring 1 (VRD)

Another Androgenic Agent (VRaA) DRUG

Testosterone 35 mg in vaginal ring

Vaginal ring 2 (VRaA)

Fixed combination of 2 androgenic agents (VR2A) DRUG

DHEA 1.5 g/testosterone 25 mg fixed combination in vaginal ring

Vaginal ring 3 (VR2A)

Eligibility Criteria

• Age: 38 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Women with preserved menstrual cycles.
• Women smoking less than 5 cigarettes daily.
• Anti-Müllerian hormone (AMH) between 0.5-1.1 ng/mL
• Total antral follicle count (AFC) 5-7

You may not qualify if:

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

Sponsors & Collaborators

• Laboratorios Andromaco S.A.: lead

Study Sites (1)

Mother and Health Research Institute (IDIMI), Faculty of Medicine, University of Chile

Santiago, International, 7501257, Chile

Location

Related Publications (9)

• 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.

  PMID: 15543027 BACKGROUND

• 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.

  PMID: 16997936 BACKGROUND

• 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.

  PMID: 16517559 BACKGROUND

• 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.

  PMID: 19589949 BACKGROUND

• 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.

  PMID: 19054777 BACKGROUND

• 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.

  PMID: 21505041 BACKGROUND

• 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.

  PMID: 20638339 BACKGROUND

• 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.

  PMID: 20091563 BACKGROUND

• 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.

  PMID: 20729538 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2014
• First Posted: October 20, 2014
• Study Start: July 15, 2014
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)