on the first study visit a baseline electrocardiogram (ecg) is performed to record the heart’s electrical activity before any hormone therapy is started.

an implantable loop recorder (ilr) is placed under the skin to continuously monitor heart rhythm throughout the study.

a questionnaire about menopausal symptoms and medical history is completed.

the patient is randomly assigned to one of the estrogen preparations that will be used for the first 4‑week treatment period.

possible estrogen options are:

• estradot patch delivering 50 µg estradiol over 24 hours, applied once daily.
• estrogel gel delivering 0.75 mg estradiol, applied once daily.
• lenzetto spray delivering 3.06 mg estradiol, applied once daily.
• estradiol oral tablet 1 mg, taken once daily.

if the study protocol requires a progesterone component, the patient will also receive either utrogestan soft capsule 100 mg or norethisterone acetate tablet 0.5 mg, both taken once daily.

for a transdermal patch, the patch is applied to clean, dry skin on the abdomen or buttock and replaced every 24 hours.

for a transdermal gel, a measured amount is spread on the skin of the upper arm or abdomen and allowed to dry before dressing.

for a transdermal spray, the spray is applied to the skin of the upper arm or abdomen once daily as directed.

for oral tablets or capsules, the dose is swallowed with water at the same time each day.

if a progesterone capsule or tablet is required, it is also taken once daily with water.

the patient continues the assigned medication for a total of 4 weeks.

regular visits (typically weekly or bi‑weekly) are scheduled for repeat ecg recordings and safety checks.

the implanted ilr continuously records heart rhythm and any ventricular arrhythmias, which are reviewed by study staff.

at the end of the 4‑week period a final ecg is performed to determine the maximum change in the corrected QT interval (qtc).

the data from the ilr are examined for any ventricular arrhythmias that occurred during the period.

the patient completes a follow‑up questionnaire about menopausal symptoms.

after the first assessment the patient stops the current medication and is randomly assigned to the next estrogen preparation, following the same dosage and frequency rules described in step 2.

if a progesterone component is required for the new regimen, the appropriate capsule or tablet is prescribed as in step 2.

the patient repeats steps 3 through 5 for each subsequent 4‑week hormone regimen.

each period is monitored in the same way, with weekly ecg checks, continuous ilr recording, and symptom questionnaires.

once all assigned hormone regimens have been completed, the active crossover phase of the study ends.

the patient’s overall data, including the maximum qtc changes for each regimen and any recorded arrhythmias, are compiled for analysis.

after the crossover phase the patient enters a long‑term observational period during which routine clinical care continues.

periodic study visits are scheduled (for example at 3, 6 and 12 months) to perform additional ecg recordings, review ilr data, and complete menopause rating scale questionnaires.

no study medication is required during this follow‑up; the patient follows the hormone therapy prescribed by the regular treating physician.