Previous studies of premenstrual syndrome (PMS) have suffered from a failure to select homogenous samples, adequately assess the detailed nature of endocrine function and account for differences in symptom severity or responses to treatment. Our overall goal is to examine the hypothesis that endogenous opiate (EO) activity will be indirectly assessed via 1) the pulsatile secretion of luteinizing hormone (LH), known to be regulated by EO, and 2) menstrual symptoms which are suspected to result from cyclic EO exposure. A repeated measures design using two, nonrandomized treatment groups will be used. Forty subjects will be recruited from PMS-diagnosed patients of a gynecologic practice who preselect either behavioral modification activities (n=20) or progesterone therapy (n-20) as the choice of treatment. Subjects will be prospectively assessed during the early follicular (EF), mid-luteal (ML) and late luteal (LL) phase of the same pretreatment cycle and in the LL of the third cycle of treatment. Studies will be performed in the Clinical Research Center of University of Michigan Hospital. At each outpatient visit, LH pulsatility will be assessed from 1 ml blood samples collected from an IV line taken at 10 min intervals for 8 hours (n=49). Cycle phase will be confirmed by measurements of estrogen and progesterone (P) levels. Serial measures of P will also be taken every 30 min at the ML and LL visits to explore its role as a regulator of EO activity. Well-established radioimmunoassays will be used for serial hormone determinations. Menstrual symptoms will be recorded each day using the Woods Daily Health Diary. The Woods Women's Health Survey will be used at entry into the study to assess psychosocial stressors, feminine socialization and health practices. LH pulsatility will be compared to that of women without PMS previously assessed by us using a similar protocol. In this way it will be possible to characterize the detailed nature of two known/suspected EO-mediated events as they are influenced by cycle phase in women with PMS. The influence of two forms of self-selected therapy interest are the psychosocial health characteristics of both treatment groups and how they may vary in relation to responsiveness to therapy. This work will provide a better understanding of the adaptational responses to PMS and should lead to more rational therapeutic interventions for its management.
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