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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Healthy Women, Infertility, Female

Intervention / Treatment
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* Drug: DHEA
* Drug: Another Androgenic Agent (VRaA)
* Drug: Fixed combination of 2 androgenic agents (VR2A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 38 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaginal ring 1 (VRD)<br>20 women using DHEA (VRD) for 2 menstrual cycles | Drug: DHEA<br>* DHEA 2.2 g in vaginal ring<br>|
| Experimental: Vaginal ring 2 (VRaA)<br>20 women using another androgenic agent (VRaA) for 2 menstrual cycles | Drug: Another Androgenic Agent (VRaA)<br>* Testosterone 35 mg in vaginal ring<br>|
| Experimental: Vaginal ring 3 (VR2A)<br>20 women using fixed combination of 2 androgenic agents (VR2A) for 2 menstrual cycles | Drug: Fixed combination of 2 androgenic agents (VR2A)<br>* DHEA 1.5 g/testosterone 25 mg fixed combination in vaginal ring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone replacement therapy