Comparison of Oral Dydrogesterone and Vaginal Progesterone in Menopausal Hormone Therapy (PRO-MHT)

Comparison of Oral Dydrogesterone and Vaginal Micronized Progesterone Regimens Combined With Transdermal Estradiol in Menopausal Hormone Therapy: A Prospective Randomized Controlled Trial

Menopause is a natural stage in a woman's life that can be associated with symptoms such as hot flashes, night sweats, sleep problems, and vaginal dryness. Menopausal hormone therapy is commonly used to relieve these symptoms. In women with an intact uterus, progesterone must be used together with estrogen to protect the lining of the uterus.

The purpose of this study is to compare two commonly used progesterone treatment methods in women receiving menopausal hormone therapy. All participants will use transdermal estradiol gel, and they will be randomly assigned to receive either oral dydrogesterone or vaginal micronized progesterone.

This prospective randomized controlled study will evaluate the effects of these treatments on endometrial thickness, menopausal symptoms, vaginal health parameters, bleeding patterns, and quality of life over a 12-month follow-up period.

The results of this study may help determine the most appropriate progesterone regimen for women undergoing menopausal hormone therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Menopausal Women; Hormone Therapy; Menopausal Symptom Relief; Menopausal Hormone Therapy
• Intervention / Treatment: Drug: Dydrogesterone 10 MG Oral Tablet; Drug: Transdermal estradiol; Drug: Micronized progesterone 200 MG

Detailed Description

Menopausal hormone therapy (MHT) is widely used for the treatment of vasomotor symptoms and genitourinary symptoms associated with menopause. In women with an intact uterus, progestogens must be administered together with estrogen therapy to prevent endometrial hyperplasia. Different progesterone formulations and routes of administration are available, including oral and vaginal preparations. However, comparative data regarding the clinical effects and endometrial safety of different progesterone regimens combined with transdermal estradiol are limited.

This prospective randomized controlled trial aims to compare two commonly used progesterone regimens in women receiving menopausal hormone therapy. All participants will receive transdermal estradiol gel and will be randomly assigned to one of two treatment groups: oral dydrogesterone or vaginal micronized progesterone. The study will follow participants for approximately 12 months.

The primary outcome of the study is endometrial thickness measured by transvaginal ultrasonography. Secondary outcomes include menopausal symptoms, quality of life assessed by validated questionnaires, vaginal health parameters such as vaginal maturation index and vaginal pH, bleeding patterns recorded in bleeding diaries, carotid intima-media thickness, and bone mineral density measurements.

The findings of this study are expected to contribute to the identification of the most appropriate progesterone regimen for women undergoing menopausal hormone therapy.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esra Ayanoglu, MD; Phone Number: +90 544 544 62 42; Email: dresraayanoglu@gmail.com
• Study Contact Backup: Name: Sevil Cankaya, MD; Phone Number: +90 505 866 34 09; Email: sevilsaltek82@gmail.com

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34785
    • Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital
    • Contact: Esra Ayanoglu, MD; Phone Number: +90 544 544 62 42; Email: dresraayanoglu@gmail.com
    • Contact: Sevil Cankaya, MD; Phone Number: +90 505 866 34 09; Email: sevilsaltek82@gmail.com
    • Principal Investigator: Esra Ayanoglu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women aged 45-60 years
• Postmenopausal status (absence of menstruation for ≥12 months)
• Intact uterus
• Presence of menopausal symptoms requiring menopausal hormone therapy
• Willingness to participate and provide written informed consent

Exclusion Criteria:

• Unexplained vaginal bleeding
• History of breast cancer or endometrial cancer
• Known hypersensitivity to study medications
• History of thromboembolic disease (e.g., deep vein thrombosis or pulmonary embolism)
• Severe liver disease
• Uncontrolled hypertension
• Any condition that, in the opinion of the investigator, makes participation inappropriate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Dydrogesterone Group; Participants will receive transdermal estradiol gel combined with oral dydrogesterone as the progesterone component of menopausal hormone therapy.	Drug: Dydrogesterone 10 MG Oral Tablet; Oral dydrogesterone will be administered in combination with transdermal estradiol as part of menopausal hormone therapy.; Other Names: Duphaston; Drug: Transdermal estradiol; Transdermal estradiol gel will be used as estrogen therapy in both treatment groups.; Other Names: Femijel
Experimental: Vaginal Micronized Progesterone Group; Participants will receive transdermal estradiol gel combined with vaginal micronized progesterone as the progesterone component of menopausal hormone therapy.	Drug: Transdermal estradiol; Transdermal estradiol gel will be used as estrogen therapy in both treatment groups.; Other Names: Femijel; Drug: Micronized progesterone 200 MG; Vaginal micronized progesterone will be administered in combination with transdermal estradiol as part of menopausal hormone therapy.; Other Names: Progestan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial Thickness	Endometrial thickness measured by transvaginal ultrasonography to evaluate endometrial safety during menopausal hormone therapy.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menopause-Specific Quality of Life (MENQOL) Score	Change in menopause-related quality of life assessed using the Menopause-Specific Quality of Life (MENQOL) questionnaire. The MENQOL is a 29-item questionnaire with scores ranging from 1 to 8 for each item, where higher scores indicate worse menopausal symptoms and lower quality of life.	Baseline and 12 months
Vaginal Maturation Index	Assessment of vaginal epithelial maturation through cytological evaluation.	Baseline and 12 months
Vaginal Symptom Score (Visual Analog Scale, VAS)	Severity of vaginal symptoms including dryness, irritation, and dyspareunia measured using a Visual Analog Scale (VAS). The VAS ranges from 0 to 10, where 0 indicates no symptoms and 10 indicates the most severe symptoms. Higher scores indicate worse symptom severity.	Baseline and 12 months
Vaginal pH	Measurement of vaginal pH as an indicator of vaginal health.	Baseline and 12 months
Number of bleeding and spotting days and proportion of participants with amenorrhea	Bleeding patterns will be evaluated using participant-recorded daily bleeding diaries. The number of bleeding and spotting days will be calculated, and the proportion of participants achieving amenorrhea will be determined.	Throughout the 12-month study period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carotid Intima-Media Thickness	Assessment of carotid artery intima-media thickness using ultrasound.	Baseline and 12 months
Bone Mineral Density	Bone mineral density measured using dual-energy X-ray absorptiometry (DEXA).	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Sehit Prof. Dr. Ilhan Varank Sancaktepe Training and Research Hospital
• Investigators: Principal Investigator: Esra Ayanoglu, Sehit Prof. Dr. Ilhan Varank Sancaktepe Training and Research Hospital

Publications and helpful links

General Publications

• Graham S, Archer DF, Simon JA, Ohleth KM, Bernick B. Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins. Gynecol Endocrinol. 2022 Nov;38(11):891-910. doi: 10.1080/09513590.2022.2118254. Epub 2022 Sep 8.
• Hipolito Rodrigues MA, Gompel A. Micronized progesterone, progestins, and menopause hormone therapy. Women Health. 2021 Jan;61(1):3-14. doi: 10.1080/03630242.2020.1824956. Epub 2020 Sep 21.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Postmenopausal women; Dydrogesterone; Endometrial thickness; Menopausal hormone therapy; Micronized progesterone; Transdermal estradiol; Progesterone route of administration
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pharmaceutical Preparations; Dosage Forms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Progesterone Congeners; Progesterone; Dydrogesterone; Tablets
• Other Study ID Numbers: AYANOGLU-MHT-RCT-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to institutional data protection policies and privacy considerations for study participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No