Efficacy of Oral Contraceptive, Progesterone, and Inositol on Menstrual Regulation in PCOS

December 10, 2025 updated by: Sabahattin Anıl Arı, Ege University

Comparison of the Efficacy of Oral Contraceptive, Progesterone, and Inositol Use in Regulating Menstrual Cycles in Patients With Polycystic Ovary Syndrome (PCOS)

This cross-sectional study aims to compare the effectiveness of oral contraceptives, oral progesterone (didrogesterone), and inositol in regulating menstrual cycles among women diagnosed with polycystic ovary syndrome (PCOS).

PCOS is a common endocrine disorder affecting reproductive-aged women and is associated with menstrual irregularities, hyperandrogenism, and polycystic ovarian morphology. While oral contraceptives are the mainstay of treatment, their use may be contraindicated in patients with cardiovascular risk factors, liver dysfunction, or in those who desire pregnancy.

This study investigates whether oral progesterone and myo-inositol can serve as effective and safer alternatives for menstrual regulation and improvement of ovarian morphology and hyperandrogenic symptoms.

A total of 150 women aged 15-40 years with a diagnosis of PCOS will be enrolled and divided into three equal groups:

Group 1: Oral contraceptive users

Group 2: Oral progesterone users

Group 3: Inositol users The study will assess changes in menstrual regularity, ovarian morphology (via ultrasound), and clinical features such as hirsutism and acne before and after treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age and is characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. It is one of the most prevalent causes of infertility and is frequently associated with metabolic abnormalities such as insulin resistance, obesity, and dyslipidemia.

The primary treatment goal in PCOS is to restore regular ovulatory cycles, improve ovarian morphology, and reduce hyperandrogenic symptoms such as hirsutism and acne.

Combined oral contraceptives (COCs) are the first-line pharmacological option for cycle regulation in PCOS; however, their use is contraindicated in women with risk factors such as smoking, thromboembolic disorders, severe hepatic dysfunction, uncontrolled hypertension, or a history of breast cancer. Additionally, COCs are not suitable for women who desire pregnancy in the near future.

Therefore, alternative treatments that can effectively regulate menstrual cycles without suppressing fertility or inducing metabolic risks are clinically relevant.

This study aims to compare the effects of oral contraceptives, oral progesterone, and myo-inositol on menstrual regulation and ovarian morphology in women diagnosed with PCOS.

A total of 150 women aged 15-40 years who meet the ESHRE/ASRM (Rotterdam) diagnostic criteria for PCOS will be enrolled at the Department of Obstetrics and Gynecology, İzmir Bakırçay University Çiğli Training and Research Hospital. Participants will be randomly assigned to one of three groups (n=50 per group):

Group 1: Oral contraceptive users

Group 2: Oral progesterone users (didrogesterone 10 mg, twice daily, cyclic regimen)

Group 3: Inositol users (2 g/day)

Clinical parameters including menstrual regularity, body mass index, hirsutism score, acne grade, and ovarian morphology (assessed via transvaginal or transabdominal ultrasonography) will be recorded at baseline and follow-up visits.

The primary outcome will be restoration of regular menstrual cycles. Secondary outcomes will include changes in ovarian morphology, reduction of hyperandrogenic symptoms, and treatment tolerability.

Data will be analyzed using appropriate parametric or non-parametric statistical tests, with significance set at p<0.05.

All patient data will be anonymized, and participation will be voluntary following written informed consent. The study has been approved by the İzmir Bakırçay University Non-Interventional Clinical Research Ethics Committee.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Turkey (Türkiye)
    • Menemen
      • Izmir, Menemen, Turkey (Türkiye), 35665
        • Recruiting
        • Izmir Bakircay University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female participants aged 18 to 40 years.
  • Diagnosed with polycystic ovary syndrome (PCOS) according to the ESHRE/ASRM (Rotterdam) criteria (presence of at least two of the following: oligo/anovulation, clinical or biochemical hyperandrogenism, polycystic ovarian morphology).
  • No significant comorbid systemic disease.
  • Willingness to participate and ability to provide written informed consent.
  • Regular follow-up availability for at least 6 months.

Exclusion Criteria:

  • Known hepatic, renal, cardiovascular, or endocrine disorders other than PCOS.
  • Pregnancy or current use of hormonal therapy within the past 3 months.
  • History of thromboembolic disease, breast cancer, or other contraindications to hormonal treatment.
  • Inability to adhere to follow-up visits or treatment regimen.
  • Severe cognitive or communication impairment that prevents proper consent or data collection.
  • Known allergy or hypersensitivity to any component of the study drugs.
  • Participation in another interventional study within the past 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Oral Contraceptive Group
Participants in this group will receive a combined oral contraceptive containing ethinylestradiol 0.03 mg and drospirenone 3 mg once daily for 21 days per cycle, followed by a 7-day pill-free interval, for 6 months. This arm serves as the active comparator to evaluate the relative efficacy of progesterone and myo-inositol therapy in menstrual regulation among women with PCOS.
Drug: Combined Oral Contraceptive (Ethinylestradiol 0.03 mg + Drospirenone 3 mg)
Participants will receive one tablet daily for 21 consecutive days, followed by a 7-day pill-free interval, for a total of 6 months. Used as the standard treatment arm for menstrual regulation in PCOS.
Experimental: Inositol Group
Participants will receive oral inositol 2g/day for 6 months. This arm will assess the ability of myo-inositol to restore ovulatory cycles, improve ovarian morphology, and reduce hyperandrogenic symptoms in PCOS compared with oral contraceptive and progesterone groups.
Dietary supplement: Inositol mid-level volume
Participants will receive oral inositol 2 g/day for 6 months to assess its effects on ovulatory function, menstrual cycle regulation, and reduction of hyperandrogenic symptoms.
Experimental: Progesterone (Didrogesterone) Group
Participants will receive oral didrogesterone 10 mg twice daily from day 15 to day 25 of each menstrual cycle for 6 months. The efficacy of didrogesterone in restoring regular menstrual cycles and improving ovarian morphology will be compared with the oral contraceptive and myo-inositol groups.
Drug: Dydrogesterone Pill

Participants will receive oral didrogesterone 10 mg twice daily from day 15 to day 25 of each menstrual cycle for 6 months (cyclic regimen).

This arm evaluates the efficacy of oral didrogesterone monotherapy in restoring regular menstruation, improving ovarian morphology, and alleviating hyperandrogenic symptoms in women with PCOS, compared with inositol and oral contraceptive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Restoration of Regular Menstrual Cycles
Time Frame: Baseline and at 6 months
Evaluation of the proportion of participants who achieve restoration of regular menstrual cycles (defined as cycle length between 25-35 days for at least three consecutive cycles) after 6 months of treatment.
Baseline and at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Ovarian Morphology
Time Frame: Baseline and at 6 months
Assessment of changes in ovarian morphology via transvaginal or transabdominal ultrasonography, including ovarian volume and follicle count, compared with baseline.
Baseline and at 6 months
Change in Serum Hormone Levels
Time Frame: Baseline and at 6 months
Comparison of baseline and post-treatment serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, and estradiol to evaluate endocrine response to each treatment.
Baseline and at 6 months
Patient Treatment Satisfaction
Time Frame: After 6 months of treatment
Self-reported patient satisfaction and tolerability using a 5-point Likert scale evaluating ease of use, perceived effectiveness, and side effects.
After 6 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ege University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Estimated)

November 21, 2025

Study Record Updates

Last Update Posted (Actual)

December 18, 2025

Last Update Submitted That Met QC Criteria

December 10, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ad-PCOS-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) that support the findings of this study will be made available to qualified researchers upon reasonable request. Data will include demographic information, treatment group, and primary/secondary outcome measures. Personally identifiable information will be removed to ensure participant confidentiality.

Data will be available after publication of the main results and upon approval by the principal investigator and the İzmir Bakırçay University Ethics Committee. Requests for access should be directed to the corresponding author via institutional email.

IPD Sharing Time Frame

From 6 months after publication to 5 years post-publication.

IPD Sharing Access Criteria

Access will be granted to researchers with methodologically sound proposals for academic and non-commercial purposes, following signing of a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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