Comparison of Oral Dydrogesterone and Vaginal Progesterone in Menopausal Hormone Therapy

NCT07496294 | Not Yet Recruiting

• 1 other identifier: AYANOGLU-MHT-RCT-2026
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Menopausal Women; Menopausal Symptom Relief; Hormone Therapy; Menopausal Hormone Therapy

Keywords

Menopausal hormone therapy; Dydrogesterone; Micronized progesterone; Transdermal estradiol; Progesterone route of administration; Endometrial thickness; Postmenopausal women; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Endometrial Thickness

  Endometrial thickness measured by transvaginal ultrasonography to evaluate endometrial safety during menopausal hormone therapy.

  12 months

Secondary Outcomes (5)

• Menopause-Specific Quality of Life (MENQOL) Score

  Baseline and 12 months

• Vaginal Maturation Index

  Baseline and 12 months

• Vaginal Symptom Score (Visual Analog Scale, VAS)

  Baseline and 12 months

• Vaginal pH

  Baseline and 12 months

• Number of bleeding and spotting days and proportion of participants with amenorrhea

  Throughout the 12-month study period

Other Outcomes (2)

• Carotid Intima-Media Thickness

  Baseline and 12 months

• Bone Mineral Density

  Baseline and 12 months

Study Arms (2)

Oral Dydrogesterone Group

EXPERIMENTAL

Participants will receive transdermal estradiol gel combined with oral dydrogesterone as the progesterone component of menopausal hormone therapy.

Drug: Dydrogesterone 10 MG Oral Tablet; Drug: Transdermal estradiol

Vaginal Micronized Progesterone Group

EXPERIMENTAL

Participants will receive transdermal estradiol gel combined with vaginal micronized progesterone as the progesterone component of menopausal hormone therapy.

Drug: Micronized progesterone 200 MG; Drug: Transdermal estradiol

Interventions

Dydrogesterone 10 MG Oral Tablet DRUG

Oral dydrogesterone will be administered in combination with transdermal estradiol as part of menopausal hormone therapy.

Also known as: Duphaston

Oral Dydrogesterone Group

Micronized progesterone 200 MG DRUG

Vaginal micronized progesterone will be administered in combination with transdermal estradiol as part of menopausal hormone therapy.

Also known as: Progestan

Vaginal Micronized Progesterone Group

Transdermal estradiol DRUG

Transdermal estradiol gel will be used as estrogen therapy in both treatment groups.

Also known as: Femijel

Oral Dydrogesterone Group; Vaginal Micronized Progesterone Group

Eligibility Criteria

• Age: 45 Years - 60 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sehit Prof. Dr. Ilhan Varank Sancaktepe Training and Research Hospital: lead

Study Sites (1)

Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital

Istanbul, 34785, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 36075250 BACKGROUND

• 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.

  PMID: 32957843 BACKGROUND

MeSH Terms

Interventions

Dydrogesterone; Tablets; Progesterone

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Esra Ayanoglu

  Sehit Prof. Dr. Ilhan Varank Sancaktepe Training and Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Esra Ayanoglu, MD

CONTACT

+90 544 544 62 42; dresraayanoglu@gmail.com

Sevil Cankaya, MD

CONTACT

+90 505 866 34 09; sevilsaltek82@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study is open-label and participants will receive one of the two progesterone regimens according to randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to receive transdermal estradiol combined with either oral dydrogesterone or vaginal micronized progesterone.

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 27, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)