Estetrol 15–25 mg Dose Range for VMS Relief and Safety

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Solution Overview

Problem

Current hormone replacement therapies for alleviating menopause-associated symptoms, particularly vasomotor symptoms (VMS), face challenges in identifying the optimal dose of estetrol that balances efficacy with minimal side effects, as higher doses can lead to adverse events like endometrial thickness changes.

Innovation Solution

The determination of a daily dose range of 15 mg to 25 mg of estetrol, considering both the frequency and severity of VMS, reveals a therapeutic window where significant symptom relief is achieved with manageable side effects, supported by the administration of estetrol in combination with progestogenic components like drospirenone or bazedoxifene.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If higher doses of estetrol are administered to improve efficacy in alleviating menopause-associated symptoms, then symptom relief is enhanced, but adverse events such as endometrial thickness changes increase

Engineering Contradiction:

Improveefficacy in alleviating VMSVSAvoidadverse events including endometrial thickness changes

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent identifies and establishes an optimal dosage range (15-25 mg daily) that represents a parameter optimization, balancing therapeutic efficacy with safety by finding the dose level that maximizes symptom relief while minimizing adverse effects on endometrial thickness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies the principle of partial action by administering estetrol at moderate doses (15-25 mg) rather than high doses, achieving sufficient therapeutic effect while avoiding the excessive dosage that would cause harmful side effects

Inventive Principle:

Principle #16Partial or excessive action

2Object-affected harmful factors

If estetrol is administered at doses below 15 mg daily, then side effects are minimized, but statistically significant relief for VMS is not achieved

Engineering Contradiction:

Improveside effectsVSAvoidstatistically significant efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent establishes a minimum effective dose threshold (15 mg daily) through parameter optimization, identifying the dosage level at which estatrol begins to produce statistically significant therapeutic effects while maintaining an acceptable safety profile

Inventive Principle:

Principle #35Parameter changes

3Reliability

If estetrol is administered at doses above 25 mg daily, then symptom relief is maximized, but the therapeutic window narrows due to increased side effects

Engineering Contradiction:

Improvesymptom reliefVSAvoidside effects reducing therapeutic window

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent defines an optimal dosage range (15-25 mg daily) through parameter optimization, establishing upper and lower bounds that maximize the therapeutic window by balancing efficacy with safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies partial action by limiting the dose to 25 mg daily maximum, achieving sufficient symptom relief without exceeding the dosage that would cause harmful side effects and narrow the therapeutic window

Inventive Principle:

Principle #16Partial or excessive action

Data Source

PatentUS12458651B2Compounds and their uses for alleviating menopause-associated symptoms

Publication Date: 2025.11.04 ESTETRA SRL

AI summary

The present invention relates to a hormone replacement therapy, to the associated compounds and to the associated packaging units, for alleviating menopause-associated symptoms which is based on the administration to a female mammal of an estetrol component at specified daily doses, optionally in combination with a progestogenic component.The therapy enjoys a statistically significant efficacy combined with a favourable profile for side effects compared to currently available methods for alleviating menopause-associated symptoms.