MON-163 - Personalized Menopausal Hormone Therapy Based on Genetic Sensitivity of Progesterone Receptors

Background:
Individual variability in response to menopausal hormone therapy (MHT) remains a clinical challenge. Even with standard regimens, some patients experience side effects or insufficient clinical benefit. Polymorphisms in steroid hormone receptor genes, affecting tissue sensitivity to progesterone, may contribute to these differences.

Objective:
To assess the clinical significance of genetic variations in progesterone receptor (PGR, PROGINS; g.101062681 C>A; c.1486 G>T) sensitivity for optimizing MHT regimens and doses. Genomic DNA was analyzed by direct sequencing.

Materials and

Methods:
Fifty women receiving MHT were included. Progesterone receptor gene polymorphisms were analyzed by direct sequencing. Forty-three patients exhibited normal receptor sensitivity, while seven had reduced sensitivity associated with rare polymorphisms. All participants received standard MHT with estrogens and progesterone at conventional doses. Clinical tolerance and adverse effects were monitored during therapy.

Results:
In the reduced-sensitivity group, 5 of 7 patients experienced mood swings, sleep disturbances, breast tenderness, and headaches. One patient developed uterine bleeding due to endometrial hyperplasia. In the normal-sensitivity group, pronounced side effects were significantly less frequent. These findings indicate that genetically determined progesterone receptor sensitivity influences both tolerability and clinical response to MHT.

Conclusion:
Genetic variations in progesterone receptor sensitivity significantly affect the safety and efficacy of MHT. Pre-treatment genetic testing can identify patients at risk for adverse effects, allowing individualized selection of therapy regimens and doses, thereby improving clinical outcomes and reducing side effects.

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