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[5] Systemically elevated estradiol exerts negative feedback on the hypothalamic-pituitary-gonadal axis, reducing secretion of luteinizing hormone and follicle-stimulating hormone, a property leveraged therapeutically in certain hypoestrogenic states to stabilize hormonal milieu and mitigate vasomotor volatility

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Some researchers prefer adding 2.5 mL for a 4 mg/mL concentration, especially when they need finer dose adjustments during dose titration phases