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

Infertility, Female Clinical Trial

Official title:

Assess the Effect of DHEA or Other Androgenic Agents on Ovarian Reserve Markers in Women With Diminished Ovarian Reserve

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02268032
• Other study ID #: DVR+T001
• Status: Completed
• Phase: Phase 1
• Start date: July 15, 2014
• Est. completion date: August 31, 2016

Study information

• Verified date: May 2019
• Source: Laboratorios Andromaco S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: August 31, 2016
• Est. primary completion date: August 31, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 38 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Women
• Infertility
• Infertility, Female

Intervention

Drug:
• DHEA
DHEA 2.2 g in vaginal ring
• Another Androgenic Agent (VRaA)
Testosterone 35 mg in vaginal ring
• Fixed combination of 2 androgenic agents (VR2A)
DHEA 1.5 g/testosterone 25 mg fixed combination in vaginal ring

Locations

Country	Name	City	State
Chile	Mother and Health Research Institute (IDIMI), Faculty of Medicine, University of Chile	Santiago	International

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorios Andromaco S.A.

Country where clinical trial is conducted

Chile, 

References & 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. Review. — View Citation

Balasch J, Fábregues F, Peñarrubia 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. Epub 2006 Mar 3. — View 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. Epub 2006 Sep 22. — View 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. Review. — View Citation

Fábregues F, Peñarrubia 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	A composite of hormones was measured and compared before and after hormonal therapy.	Before therapy start and up to 2 months thereafter
Secondary	Tolerability of using the vaginal ring	A questionnaire was used post insertion and post extraction of the vaginal ring to assess tolerability. The following was addressed: changes in vaginal discharge (never happened/no change/increased a little/increased much/changed color), vaginal infection (by fungi or bacteria: yes/no), burning (yes/no), odor (yes/no), pain (yes/no; if yes, assessed on a 1 to 10 scale for no pain to worst pain), discomfort (yes/no) or dryness (yes/no) of the vagina, changes (for couples) in the sexual relationship by the use of the vaginal ring (better/as always/with annoyance/with pain/did not have).	After therapy start (vaginal ring insertion) and after 2 months (ring extraction)
Secondary	Number of subjects with adverse events per treatment group	Adverse events were collected by non-leading questions.	From therapy start to up to 2 months