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

Phase 1

Completed

• Conditions: Healthy Women; Infertility, Female
• Interventions: Drug: Another Androgenic Agent (VRaA); Drug: Fixed combination of 2 androgenic agents (VR2A); Drug: DHEA

• Registration Number: NCT02268032
• Lead Sponsor: Laboratorios Andromaco S.A.

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

Study Timeline

• Study Start: 2014-07-15
• Study First Submitted: 2014-08-25
• Study First Submitted QC: 2014-10-17
• Study First Posted: 2014-10-20
• Primary Completion: 2016-08-31
• Study Completion: 2016-08-31
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-27
• Last Update Posted: 2019-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 94

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaginal ring 2 (VRaA)	Another Androgenic Agent (VRaA)	20 women using another androgenic agent (VRaA) for 2 menstrual cycles
Vaginal ring 3 (VR2A)	Fixed combination of 2 androgenic agents (VR2A)	20 women using fixed combination of 2 androgenic agents (VR2A) for 2 menstrual cycles
Vaginal ring 1 (VRD)	DHEA	20 women using DHEA (VRD) for 2 menstrual cycles

Primary Outcome Measures

Name	Time	Method
Effect of the association of DHEA plus testosterone over ovarian reserve markers	Before therapy start and up to 2 months thereafter	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.

Secondary Outcome Measures

Name	Time	Method
Number of subjects with adverse events per treatment group	From therapy start to up to 2 months	Adverse events were collected by non-leading questions.
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	A composite of hormones was measured and compared before and after hormonal therapy.
Tolerability of using the vaginal ring	After therapy start (vaginal ring insertion) and after 2 months (ring extraction)	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).

Trial Locations

Locations (1)

Mother and Health Research Institute (IDIMI), Faculty of Medicine, University of Chile; 🇨🇱 Santiago, International, Chile