New hormone pill cuts hot flashes in half for menopausal women

NCT ID NCT04090957

Symptom relief Sponsor: Estetra Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This phase 3 trial tested whether estetrol (E4), a type of estrogen, can reduce hot flashes and night sweats in women going through menopause. Over 1,000 women took either 15 mg, 20 mg, or a placebo daily for 12 weeks. The study measured how often and how severe their symptoms were. Results showed that estetrol helped lower both the frequency and severity of hot flashes compared to placebo.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

1,015 people

The number who actually took part.

Started

Sep 2019

Finished

Aug 2022

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

40 to 65 years

Sex

Female participants only

Healthy volunteers

Accepted

You do not need to have the condition being studied to take part.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Signed and dated written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, after the nature of the trial has been explained according to local regulatory requirements; 2. Females ≥ 40 up to ≤ 65 years of age at randomization/treatment allocation; 3. For hysterectomized subjects: documented hysterectomy must have occurred at least 6 weeks prior to the start of screening. Hysterectomy can be total or subtotal (i.e., cervix was not removed). 4. For non-hysterectomized subjects: uterus with bi-layer endometrial thickness ≤ 4 mm on transvaginal ultrasound (TVUS) 5. For non-hysterectomized subjects: endometrial biopsy taken during screening that reveals no abnormal result, i.e., presence of hyperplasia (simple or complex, with or without atypia), presence of carcinoma, and presence of disordered proliferative endometrium findings. The screening biopsy should have sufficient endometrial tissue for diagnosis. Biopsies without tissue or with insufficient tissue may be repeated once; 6. Seeking treatment for relief of VMS associated with menopause; 1. For the Efficacy Study part: at least 7 moderate to severe bothersome VMS per day or at least 50 moderate to severe bothersome VMS per week in the last 7 consecutive days during the Screening period; 2. For the Safety Study part: at least 1 moderate to severe VMS per week; 7. Body mass index ≥ 18.0 kg/m² up to ≤ 38.0 kg/m²; 8. A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening; 9. Post-menopausal status defined as any of the following: 1. For non-hysterectomized subjects: * At least 12 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) \>40 milli-International unit (mIU)/mL (value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20); * or at least 6 months of spontaneous amenorrhea with serum FSH \>40 mIU /mL and E2 \<20 pg/mL (value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20); * or at least 6 weeks postsurgical bilateral oophorectomy; 2. For hysterectomized subjects: * serum FSH \>40 mIU/mL and E2 \<20 pg/mL (values obtained after washout of estrogen/progestin containing drug, see exclusion criteria 18 and 20); * or at least 6 weeks post-surgical bilateral oophorectomy; 10. Good physical and mental health, in the judgement of the Investigator as based on medical history, physical and gynecological examination, and clinical assessments performed prior to Visit 1; 11. Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions; 12. Able and willing to complete trial daily diaries and questionnaires. Exclusion Criteria: 1. History of malignancy, with the exception of basal cell or squamous cell carcinoma of the skin if diagnosed more than 1 year prior to the Screening visit; 2. Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (however, simple cysts confirmed by ultrasound are allowed); 3. Papanicolaou (PAP) test with atypical squamous cells undetermined significance (ASC-US) or higher (low-grade squamous intraepithelial lesion \[LSIL\], atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion \[HSIL\] \[ASC-H\], HSIL dysplastic or malignant cells) in sub-totally hysterectomized and non-hysterectomized subjects. Note: ASC-US is allowed if a reflex human papilloma virus (HPV) testing is performed and is negative for high risk oncogene HPV subtypes 16 and 18; 4. For non-hysterectomized subjects: 1. History or presence of uterine cancer, endometrial hyperplasia, or disordered proliferative endometrium; 2. Presence of endometrial polyp; 3. Undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding; 4. Endometrial ablation; 5. Any uterine/endometrial abnormality that in the judgment of the investigator contraindicates the use of estrogen and/or progestin therapy. This includes presence or history of adenomyosis or significant myoma; 5. Systolic blood pressure (BP) higher than 130 mmHg, diastolic BP higher than 80 mmHg during screening; 6. History of venous or arterial thromboembolic disease (e.g., superficial or deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, angina pectoris, etc.), or first-degree family history of venous thromboembolism (VTE); 7. History of known acquired of congenital coagulopathy or abnormal coagulation factors, including known thrombophilia's; 8. Laboratory values of fasting glucose above 125 mg/dL and/or glycated hemoglobin above 7%; 9. Dyslipoproteinaemia (LDL \>190 mg/dL and/or triglycerides \>300 mg/dL); 10. Subjects smoking \>15 cigarettes per day; 11. Presence or history of gallbladder disease, unless cholecystectomy has been performed; 12. Systemic lupus erythematosus; 13. Any malabsorption disorders including gastric bypass surgery; 14. History of acute liver disease in the preceding 12 months before the start of screening or presence or history of chronic or severe liver disease \[alanine transaminase (ALT) or aspartate transaminase (AST) \>2 x upper limit of normal (ULN), bilirubin \>1.5 ULN\], or liver tumors; 15. Chronic or current acute renal impairment (estimated glomerular filtration rate \<60 ml/min); 16. Porphyria; 17. Diagnosis or treatment of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, etc.) in the judgement of the Investigator; 18. Use of estrogen/progestin containing drug(s) up to: 1. 1 week before screening start for vaginal non-systemic hormonal products (rings, creams, gels); 2. 4 weeks before screening start for vaginal or transdermal estrogen or estrogen/progestin products; 3. 8 weeks before screening start for oral estrogen and/or progestin products and/or selective estrogen receptor modulator therapy; 4. 8 weeks before screening start for intrauterine progestin therapy; 5. 3 months before screening start for progestin implants or estrogen alone injectable drug therapy; 6. 6 months before screening start for estrogen pellet therapy or progestin injectable drug therapy; 19. Use of androgen/dehydroepiandrosterone (DHEA) containing drugs: 1. 8 weeks before screening start for oral, topical, vaginal or transdermal androgen; 2. 6 months before screening start for implantable or injectable androgen therapy; 20. Use of phytoestrogens or black cohosh for treatment of VMS up to 2 weeks before the start of screening; 21. For the women participating in the Efficacy Study part: use of prescription or over-the-counter products used for the treatment of VMS, e.g., anti-depressants: paroxetine, escitalopram, methyldopa, opioid and clonidine up to 4 weeks before the start of screening, and venlafaxine and desvenlafaxine up to 3 months before the start of screening , and not willing to stop these during their participation in the trial; 22. Not willing to stop any hormonal products as described in exclusion criteria 18, 19 and 20 during their participation in the trial; 23. Inadequately treated hyperthyroidism with abnormal thyroid stimulating hormone (TSH) and free T4 at screening. Subjects with low or high TSH are allowed if free T4 at screening is within normal range; 24. History or presence of allergy/intolerance to the investigational product or drugs of this class or any component of it, or history of drug or other allergy that, in the opinion of the Investigator contraindicates subject participation; 25. For non-hysterectomized subjects: history or presence of allergy to peanuts; 26. History of alcohol or substance abuse (including marijuana, even if legally allowed) or dependence in the previous 12 months before the start of screening as determined by the Investigator, based on reported observations; 27. Sponsor or contract research organization (CRO) employees or employees under the direct supervision of the Investigator and/or involved directly in the trial; 28. Subjects with known or suspected history of a clinically significant systemic disease, unstable medical disorders, life-threatening disease or current malignancies that would pose a risk to the subject in the opinion of the Investigator; 29. Participation in another investigational drug clinical trial within 1 month (30 days) or having received an investigational drug within the last month (30 days) before the start of screening; 30. Is judged by the Investigator to be unsuitable for any reason.

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Conditions

The condition(s) this trial relates to.

Hot Flashes

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Menopausal symptoms Vasomotor symptoms

Contacts and locations

Locations

Estetra Study Site

Birmingham, Alabama, 35205, United States
Estetra Study Site

Birmingham, Alabama, 35218, United States
Estetra Study Site

Birmingham, Alabama, 35235, United States
Estetra Study Site

Dothan, Alabama, 36303-1928, United States
Estetra Study Site

Phoenix, Arizona, 85018, United States
Estetra Study Site

Phoenix, Arizona, 85032, United States
Estetra Study Site

Tempe, Arizona, 85281, United States
Estetra Study Site

Tucson, Arizona, 85704, United States
Estetra Study Site

Tucson, Arizona, 85712, United States
Estetra Study Site

Tucson, Arizona, 85715, United States
Estetra Study Site

Tucson, Arizona, 85745, United States
Estetra Study Site

Little Rock, Arkansas, 72204, United States
Estetra Study Site

Bellflower, California, 90706, United States
Estetra Study Site

Canoga Park, California, 91303, United States
Estetra Study Site

Chula Vista, California, 91911, United States
Estetra Study Site

Huntington Beach, California, 92647, United States
Estetra Study Site

La Mesa, California, 91942, United States
Estetra Study Site

Lincoln, California, 95648, United States
Estetra Study Site

Los Angeles, California, 90057, United States
Estetra Study Site

Pomona, California, 91767, United States
Estetra Study Site

Sacramento, California, 95821, United States
Estetra Study Site

San Diego, California, 92111, United States
Estetra Study Site

San Diego, California, 92120, United States
Estetra Study Site

Santa Ana, California, 92705, United States
Estetra Study Site

Thousand Oaks, California, 91360, United States
Estetra Study Site

West Covina, California, 91790, United States
Estetra Study Site

Colorado Springs, Colorado, 80918, United States
Estetra Study Site

Denver, Colorado, 80209, United States
Estetra Study Site

Crystal River, Florida, 34429, United States
Estetra Study Site

Jacksonville, Florida, 32207, United States
Estetra Study Site

Jacksonville, Florida, 32256, United States
Estetra Study Site

Miami, Florida, 33134, United States
Estetra Study Site

Miami, Florida, 33155, United States
Estetra Study Site

Miami, Florida, 33173, United States
Estetra Study Site

Miami Lakes, Florida, 33014, United States
Estetra Study Site

New Port Richey, Florida, 34653, United States
Estetra Study Site

Ocoee, Florida, 34761, United States
Estetra Study Site

Orlando, Florida, 32801, United States
Estetra Study Site

Sarasota, Florida, 34239-3132, United States
Estetra Study Site

West Palm Beach, Florida, 33409, United States
Estetra Study Site

Atlanta, Georgia, 30342, United States
Estetra Study Site

Morrow, Georgia, 30260, United States
Estetra Study Site

Sandy Springs, Georgia, 30328, United States
Estetra Study Site

Savannah, Georgia, 31406, United States
Estetra Study Site

Idaho Falls, Idaho, 83404, United States
Estetra Study Site

Meridian, Idaho, 83642, United States
Estetra Study Site

Evansville, Indiana, 47714, United States
Estetra Study Site

Marrero, Louisiana, 70072, United States
Estetra Study Site

Saginaw, Michigan, 48602, United States
Estetra Study Site

Saginaw, Michigan, 48604, United States
Estetra Study Site

Rochester, Minnesota, 55905, United States
Estetra Study Site

St Louis, Missouri, 63141, United States
Estetra Study Site

Lincoln, Nebraska, 68510, United States
Estetra Study Site

Norfolk, Nebraska, 68701, United States
Estetra Study Site

Las Vegas, Nevada, 89106, United States
Estetra Study Site

Las Vegas, Nevada, 89128, United States
Estetra Study Site

Albuquerque, New Mexico, 87102, United States
Estetra Study Site

Albuquerque, New Mexico, 87109-4640, United States
Estetra Study Site

New York, New York, 10032, United States
Estetra Study Site

Charlotte, North Carolina, 28209, United States
Estetra Study Site

Charlotte, North Carolina, 28277, United States
Estetra Study Site

Columbus, North Carolina, 28412, United States
Estetra Study Site

Fayetteville, North Carolina, 28304, United States
Estetra Study Site

Hickory, North Carolina, 28601, United States
Estetra Study Site

New Bern, North Carolina, 28562, United States
Estetra Study Site

Raleigh, North Carolina, 27609, United States
Estetra Study Site

Raleigh, North Carolina, 27612, United States
Estetra Study Site

Rocky Mount, North Carolina, 27804, United States
Estetra Study Site

Cincinnati, Ohio, 45212, United States
Estetra Study Site

Cincinnati, Ohio, 45267, United States
Estetra Study Site

Cleveland, Ohio, 44122, United States
Estetra Study Site

Columbus, Ohio, 43213, United States
Estetra Study Site

Columbus, Ohio, 43231, United States
Estetra Study Site

Fairfield, Ohio, 45014, United States
Estetra Study Site

Erie, Pennsylvania, 16507, United States
Estetra Study Site

Philadelphia, Pennsylvania, 19114, United States
Estetra Study Site

Bluffton, South Carolina, 29910, United States
Estetra Study Site

Columbia, South Carolina, 29201, United States
Estetra Study Site

Mt. Pleasant, South Carolina, 29464, United States
Estetra Study Site

Myrtle Beach, South Carolina, 29572, United States
Estetra Study Site

North Charleston, South Carolina, 29405, United States
Estetra Study Site

Chattanooga, Tennessee, 37404, United States
Estetra Study Site

Jefferson City, Tennessee, 37760, United States
Estetra Study Site

Knoxville, Tennessee, 37912, United States
Estetra Study Site

Knoxville, Tennessee, 37938, United States
Estetra Study Site

Memphis, Tennessee, 38119, United States
Estetra Study Site

Memphis, Tennessee, 38120, United States
Estetra Study Site

Dallas, Texas, 75251, United States
Estetra Study Site

Fort Worth, Texas, 76104, United States
Estetra Study Site

Fort Worth, Texas, 76140, United States
Estetra Study Site

Georgetown, Texas, 78626, United States
Estetra Study Site

Houston, Texas, 77023, United States
Estetra Study Site

Houston, Texas, 77024, United States
Estetra Study Site

Houston, Texas, 77054, United States
Estetra Study Site

Houston, Texas, 77081, United States
Estetra Study Site

Houston, Texas, 77084, United States
Estetra Study Site

Houston, Texas, 77099, United States
Estetra Study Site

McAllen, Texas, 78503, United States
Estetra Study Site

McAllen, Texas, 78504, United States
Estetra Study Site

Pearland, Texas, 77581, United States
Estetra Study Site

Plano, Texas, 75093, United States
Estetra Study Site

San Antonio, Texas, 78258, United States
Estetra Study Site

Draper, Utah, 84020, United States
Estetra Study Site

Pleasant Grove, Utah, 84062, United States
Estetra Study Site

West Jordan, Utah, 84088, United States
Estetra Study Site

Charlottesville, Virginia, 22911, United States
Estetra Study Site

Norfolk, Virginia, 23507, United States
Estetra Study Site

Virginia Beach, Virginia, 23456, United States
Estetra Study Site

Bellevue, Washington, 98007, United States
Estetra Study Site

Seattle, Washington, 98105, United States
Estetra Study Site

Morgantown, West Virginia, 26505, United States
Estetra Study Site

Red Deer, Alberta, T4P 1K4, Canada
Estetra Study Site

Montreal, Quebec, H4P 2S4, Canada
Estetra Study Site

Brampton, L6T 0G1, Canada
Estetra Study Site

Québec, G1N 4V3, Canada
Estetra Study Site

Québec, G1S 2L6, Canada
Estetra Study Site

Waterloo, N2J 1C4, Canada

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