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It requires higher doses of estrogen and is riskier than the current standard of care.

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The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation.

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This regimen started with normal doses of estrogen and anti-androgen, then increased the anti-androgen above normal dosage by adding another, less effective anti-androgen.

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The rationale for this four-phasic regimen based on an estrogen stepdown and progestin stepup is that early estrogen dominance would confer endometrial proliferation in the first half of the cycle and prepare the endometrium for a midcyclic progestin effect.

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