Comparison of Hormonal Therapy: Mediating Hot Flashes Tapering Regimens for Mediating Hot Flashes

Study Overview
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Brief Summary
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This study will evaluate whether there is a difference in the proportion of women who report a worsening severity of their hot flashes between three tapering schedules for one accepted HT/ET regimen. Secondarily, we hope to evaluate whether there is a difference in the frequency (number of occurrences per week), severity (defined as a subjective scale mild, moderate, or severe), and Severity Index (SI, equaling the product of both) of hot flashes between three tapering schedules for one accepted HT/ET regimen.

Detailed Description
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A Comparison of Hormonal Therapy: Tapering Regimens for Mediating Hot Flashes Clinicians have been asking for years whether a tapering dose of HT would make a difference in the frequency and severity of vasomotor symptoms after menopausal women stop HT therapy. This planned randomized, placebo-controlled trial (RCT) seeks to evaluate whether there is a difference in the proportion of women who report a worsening severity of their hot flashes between three tapering schedules for one accepted HT/ET regimen. Secondarily, we hope to evaluate whether there is a difference in the frequency (number of occurrences per week), severity (defined as a subjective scale mild, moderate, or severe), and Severity Index (SI, equaling the product of both) of hot flashes between three tapering schedules for one accepted HT/ET regimen. All participants will be randomized to one of the three arms (taper arm, placebo arm, and cold turkey arm). Each patient's gynecologist will be aware of the patient's involvement in the study and will assist by providing baseline safety information. All patients will be taken off their current HT/ET regimen and will be placed on study medication (1 mg of Estradiol PO every day for 8 weeks, stabilization phase). After the 8-week stabilization period, all participants will begin the therapy corresponding to the arm to which they were randomized. Each patient in the taper or placebo arm will take one capsule per day. The patients in the cold turkey arm will discontinued acutely after the stabilization. The patients will keep a diary of the number and frequency of symptoms during the study. Patients will be contacted by phone to confirm that they are completing their diaries and that they have not developed side effects or complications that could force their discontinuation from the study. Patients will be followed for several additional weeks, after discontinuation from treatment or placebo, to monitor for symptoms. At the end of the study, our coordinator will contact the patient to assure that Medroxyprogesterone acetate, MPA, was taken properly by those women who have a uterus. They will also confirm that no other symptoms, complications, or questions have arisen. At that time, they will be able to return to their prior therapy as deemed appropriate by them and their physician. Patients will be recruited by invitation upon presenting for care to their physician. With invitations at recruitment, all patients will be given a study form. Reasons for ineligibility or refusal will be noted. After expressing interest, the physician or practice of record will sign a form acknowledging that their patient has had an annual physical exam (including pelvic exam) within the last 12 months and that a mammogram has been reported as negative (BIRADS I or II) within the last 24 months. An appointment will be made with one of our study personnel or coordinators. The patient will bring the signed form to this visit. At this enrollment / consent visit, their eligibility criteria will be reviewed. All patients will sign the informed consent, and be randomized to a group.

Official Title
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A Comparison of Hormonal Therapy: Tapering Regimens for Mediating Hot Flashes

Conditions
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Hot Flashes, Night Sweats

Intervention / Treatment
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* Drug: Estradiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female. ages 35-70, inclusive. Postmenopausal (Natural or surgical: see definitions). Currently on HT/ET for at least 6 months for vasomotor symptomatology. Vasomotor symptoms are currently controlled on medication . An annual physical & pelvic exam has been performed within the last 12mo The patient has had a normal mammogram(BIRADS I/II) within the last 24mo Exclusion Criteria: Males Hypertension, defined as either SBP >140 mmHg or DBP >90 mmHg Lack of compliance (willingness to adhere to protocol) Inability or unwillingness to swallow pills Patients with any contraindications to HT/ET

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Group A will be tapered over 4 weeks, starting at baseline (week 0). Subjects in this group will take one tablet of ET daily (effective dose, 0.75 mg) for week 1, then one 0.50 mg tablet daily for week 2, then one 0.25 mg tablet daily for week 3, and finally one 0.125 mg tablet daily for week 4. | Drug: Estradiol<br>* 1mg during stabilization & then a taper to 0.75mg, 0.5mg, 0.25mg, 0.125mg.<br>|
| Placebo Comparator: 2<br>Group B will be administered placebo. These tablets will appear identical to those administered to subjects in Group A, but the tablets will contain no estrogen. Subjects in this group will be instructed to take one pill every day for the 4 weeks. Thus, while patients will, in effect, be stopped abruptly from their therapy, there is still the potential of a placebo effect. | Drug: Estradiol<br>* 1mg during stabilization & then a taper to 0.75mg, 0.5mg, 0.25mg, 0.125mg.<br>|
| No Intervention: 3<br>Group C will have their therapy discontinued acutely at baseline (week 0); i.e., these subjects will not take any tablets after the 8-week stabilization phase ends. While we recognize that this group will not be blinded to the regimen they are receiving, we feel that group C will be important to include in light of the consistent decrease in vasomotor symptoms experienced by women taking placebo. Because women taking placebo have approximately a 35% decrease in vasomotor symptoms, it will be important to compare our taper regimen to the real life scenario of stopping medication abruptly. | Drug: Estradiol<br>* 1mg during stabilization & then a taper to 0.75mg, 0.5mg, 0.25mg, 0.125mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate whether there is a difference in the proportion of women who report a worsening severity of their hot flashes between three tapering schedules for one accepted HT/ET regimen. |  | During the tapering and post taper time period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency, severity, and Severity Index of hot flashes. |  | During the tapering and post taper time period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause, Hot flashes, vasomotor symptoms, tapering regimen, hormonal therapy, Other menopausal symptoms including mood changes