Longitudinal evaluation of activated protein C resistance among normal pregnancies of Hispanic women.

OBJECTIVE: This study was undertaken to describe pregnancy-associated activated protein C resistance and the presence of the factor V Leiden mutation in a sample population of pregnant Hispanic women. STUDY DESIGN: Twenty healthy Hispanic women with single intrauterine pregnancies were randomly selected. Blood samples were taken before 8 weeks' gestation, every 4 weeks during pregnancy, and at 6 weeks post partum. Samples were collected, separated, and stored at -70 degrees C until assay. Standard and modified partial thromboplastin time-based assays were used to evaluate response to activated protein C. A sensitivity ratio < or =2 indicated resistance to activated protein C. Repeated measures analysis of variance and unpaired t tests were used as appropriate. P <.05 was considered significant. RESULTS: Mean (+/-SEM) maternal age was 29 +/- 5 years, and most women were multiparous. Mean gestational age at delivery was 38 weeks' gestation, and the mean birth weight was 3000 g. According to the standard assay, 10 women (50%) acquired activated protein C resistance by 13 weeks' gestation, and this condition persisted through delivery and resolved post partum. Another two had preexisting activated protein C resistance. Results of the standard assay were significantly different for women with preexisting and pregnancy-associated activated protein C resistance (1.55 vs 2.18; P =.01). The modified assay distinguished between women with preexisting and pregnancy-associated activated protein C resistance at 8 weeks' gestation, 24 weeks' gestation, and post partum. The pregnancies of the women with preexisting activated protein C resistance were complicated by oligohydramnios at 34 weeks' gestation and required delivery at 36 weeks' gestation. One infant was small for gestational age. Allele-specific polymerase chain reaction analysis demonstrated that both patients with preexisting activated protein C resistance carried one copy of the factor V Leiden mutation. CONCLUSION: The incidences of pregnancy-associated and factor V Leiden mutation-associated activated protein C resistances in our cohort of gravid Hispanic women was higher than previously reported. Factor V Leiden-associated activated protein C resistance in two patients was associated with adverse perinatal outcome.

Decreased central opioid activity in premenstrual syndrome: luteinizing hormone response to naloxone.

OBJECTIVE: To evaluate central opioid activity in women with prospectively documented premenstrual syndrome (PMS) and control women in the mid- and late luteal phases of the menstrual cycle. METHODS: Blood was collected every 15 minutes 1 hour before (0800) and 2 hours after treatment (0900-1100). The treatment was administered in a randomized fashion and consisted of naloxone 1 or 4 mg or placebo, and blood was assayed for luteinizing hormone (LH). Baseline estradiol, progesterone, and prolactin were measured at 0800 and 0900 hours. RESULTS: There was a significant increase in LH area under the curve and mean LH in response to naloxone in the midluteal phase in the control (P < .001). The PMS subjects did not display a significant increase in LH concentration in response to naloxone in the midluteal phase. There were no significant LH responses to naloxone in either group in the late luteal phase. There were no significant differences in estradiol, progesterone, or prolactin concentrations or estrogen to progesterone ratios between groups. CONCLUSION: Control women have an enhanced central opioid tone during the midluteal phase that diminishes and becomes minimal in the late luteal phase of the menstrual cycle. In contrast, women with PMS have a loss of central opioid tone during the midluteal phase as indicated by the loss of LH response to naloxone. This attenuated central opioid tone in women with PMS as compared with asymptomatic control women may play a role in the pathophysiology of PMS.