Standardizing for the Menstrual Cycle Phase I and Early Phase II

Of much greater concern is the issue of standardizing the drug administration to the menstrual cycle. Women of child-bearing age do not all have cycles for the same length of days; variations of 24-36 day cycles are not unusual between and within the same women. Thus, unless controlled by oral contraceptives (OC), women volunteers could not start and finish in a study all together. Indeed, if OC were used to standardize cycles, the issue of how really representative of all women of child-bearing age this artificial hormone-boosted group might be would be debatable. Evidence suggests that even low-dose contraceptives can affect metabolism (Abernathy and Greenblatt, 1981). The logistics of running Phase I single-dose and multiple-dose ranging studies while controlling for a natural menstrual cycle are truly horrendous, both for the Phase I testing units and for the volunteer. The duration of any study would be extended by at least 1 month (the time required for the last patient's cycle to start), and each patient volunteer would have to be measured separately because of the different days of her cycle. A small but frequently argued point is timing. Which is the preferred day in the cycle for single-dose studies? And for a multiple-dose study (usually only 10-14 days long), which segments of the cycle should be covered? This may seem academic, but in those clinically significant drug classes where womens' responses to drug handling are different to those of men because of biochemical hormone effects (not just gender), then the timing of drug dosing and measurement would be critical.

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