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Drospirenone + ethinylestradiol + fluoxetine is a combination therapy being investigated by Cairo University for the treatment of severe premenstrual syndrome (PMS). This regimen combines a fourth-generation combined oral contraceptive (COC), specifically Yasmin (containing the progestin drospirenone and the estrogen ethinylestradiol), with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Drospirenone acts as a progesterone receptor agonist to inhibit ovulation and a mineralocorticoid receptor antagonist to reduce water retention, while ethinylestradiol provides estrogenic support. Fluoxetine targets the serotonin transporter (SERT) to increase synaptic serotonin levels, addressing the neuropsychiatric symptoms of PMS. The trial evaluates whether the synergistic effect of hormonal stabilization and serotonergic modulation provides superior relief compared to monotherapy or placebo.
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