Relationships among premenstrual symptoms and menstrual cycle characteristics.

The severity of premenstrual syndrome symptoms has been described by different investigators as varying directly or inversely with the severity of dysmenorrhea. In a large population of women undergoing comprehensive psychological and medical evaluation for premenstrual syndrome complaints, the authors examined the relationship between menstrual cycle parameters and premenstrual syndrome. The severity of premenstrual symptoms varied directly with the severity of dysmenorrhea and premenstrual spotting but was not associated with any other menstrual cycle parameter. Multivariate analysis revealed that social and psychological variables are more strongly associated with variations in premenstrual symptoms than are any menstrual cycle parameters.

Bioavailability of nasally administered progesterone.

PIP: 8 healthy women volunteers between the ages of 22-38 participated in a study designed to explore the relationship between endogenous estradiol (E2) levels and progesterone (P) absorption. Physical and pelvic examinations and laboratory screening tests revealed no abnormalities. All women had regular menstrual cycles, at 24-32-day intervals, and all were free of a significant menstrual cycle symptoms. 2 studies were performed at least 72 hours apart in the follicular phase of the menstrual cycle. The following medications were administered in random order: nasal P (Pronasone), 20 mg and nasal P (Pronasone), 30 mg. Serum P levels were drawn at the following times: 0, 3, 6, 10, 20, 30, 60, 120, 180, 240, 360, and 480 minutes. Serum for E2 assay was taken from the 0 time sample. The women were examined with a nasal speculum after each nasal absorption study. Serum was separated and frozen for subsequent assay. The data were analyzed using the CLINFO system from the National Institutes of Health. All of the women complained of a mildly unpleasant taste within several minutes following Pronasone administration. No evidence of nasal irritation was observed in any woman. The similar absorption curves obtained with Pronasone 20 mg and 30 mg doses and the aberrantly high values and delayed peaks ob tained in 2 subjects with the 30 mg dose imply that further work on dosage range, ointment formulation, and the method of application may be necessary before dependable clinical utility can be demonstrated. The peak levels of P that were reached compare favorably with results using similar doses (25 mg) in cocoa butter rectal or vaginal suppositories but are somewhat lower than those seen with polyethylene glycol base suppositories. The apparent inverse relationship between serum E2 levels and P levels obtained with Pronasone in the 20-mg dose was not expected. Alterations of nasal vascularity, interstitial hydration, and mucous blanket production all might influence absorption. The study demonstrates that the intranasal route is a potentially useful approach for the administration of unmodified sex steroid medications and is likely to be clinically safe and acceptable to patients.^ieng

Menstrual cycle effects on caffeine elimination in the human female.

Increases in the levels of sex steroids due to pregnancy or oral contraceptive steroid use are known to decrease significantly the rate at which caffeine is eliminated from the body. An investigation has now been made into whether the changes in sex steroid levels that occur during normal menstrual cycling also affect the rate of caffeine elimination, especially whether hormonal shifts in the luteal phase are associated with slower elimination of caffeine. Repeated 24-hour caffeine elimination studies were conducted during the follicular and luteal phases of the menstrual cycle in 10 healthy women. Comparisons of the follicular and luteal phases revealed that systemic clearance of caffeine was slower in the luteal phase, although the t1/2 did not differ. The slowing effect was related to the proximity to onset of menstruation and to levels of progesterone. The evidence suggests that caffeine elimination may be slowed in the late luteal phase, prior to the onset of menstruation. Such a reduction would lead to increased accumulation of caffeine with repeated self-administration during the day, but the effect may be too small to be of clinical significance in the majority of women.