The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination.

OBJECTIVE: To report a rare case of sequential bilateral adnexal torsion in a pregnant woman after a single cycle of gonadotropin ovulation induction with IUI. To review the literature with regards to the causation and aspects of the management of adnexal torsion, particularly after assisted conception. DESIGN: Case report. SETTING: Fertility department within a teaching hospital. PATIENT(S): A 35-year-old woman with a twin pregnancy after a cycle of gonadotropin ovulation induction and IUI. INTERVENTION(S): Gonadotropin ovulation induction with IUI; two laparotomies, salpingo-oophorectomy, stabilization of adnexa with stay suture. RESULT(S): Continuation of pregnancy until 37 weeks gestation with the abdominal delivery of healthy twins. CONCLUSION(S): The case of a woman with a multiple pregnancy and ovarian hyperstimulation syndrome after ovulation induction and IUI who developed sequential bilateral adnexal torsion is used to illustrate the risk factors and management options for adnexal torsion. Physicians should be aware of the increased incidence of adnexal torsion in the rising number of women undergoing ovulation induction in order to effect early surgical intervention and adnexal salvage. Consideration should be given to the anchoring of bulky adnexae to prevent torsion recurrence.

Bone loss after hysterectomy with ovarian conservation.

OBJECTIVE: To examine the long-term effects of hysterectomy with conservation of the ovaries on bone density of the lumbar spine and proximal femur. METHODS: A cross-sectional study of the bone density of 40 postmenopausal women who had undergone hysterectomy with ovarian conservation before menopause compared with a matched group of 40 women who had not had hysterectomy. The 40 women who had undergone hysterectomy were also compared with a control population, using multiple linear regression analysis. Bone density of the femoral neck and lumbar spine was measured by quantitative digital radiography. RESULTS: Bone density in the hysterectomy group was significantly reduced at the spine (P < .05) and at the femoral neck (P < .05) compared with the matched group. Comparisons of the hysterectomy group with the reference group demonstrated that in addition to significant reductions in bone density at the spine (P < .05) and hip (P < .05), bone density at the femoral neck (P < .05), trochanter (P < .05), Ward's triangle (P < .05), and the second (P < .05) and fourth (P < .05) lumbar vertebrae was also significantly less in the hysterectomy group. CONCLUSION: Premenopausal women who have hysterectomy will have significantly lower bone density than controls, despite conservation of both ovaries at the time of surgery.

Umbilical cord blood erythroblast count as an index of intrauterine hypoxia.

The relation of umbilical cord blood arterial pH, Apgar score, leucocyte count, and erythroblast count at delivery with the diagnosis of fetal distress in labour was studied prospectively in three groups of singleton pregnancies delivering at term vaginally (55 infants), by elective caesarean section (39 infants), or by emergency caesarean section for abnormal intrapartum fetal heart rate patterns (55 infants). In the emergency caesarean section group the umbilical cord blood arterial pH was significantly lower and the leucocyte and erythroblast counts were higher than in the elective caesarean section group. Comparison of the emergency caesarean section and spontaneous vaginal delivery groups showed significant differences for pH and erythroblast count, but not for leucocyte count. In the spontaneous vaginal delivery group erythroblastosis was associated with umbilical cord blood pH, whereas leucocytosis was associated with the length of labour. The five minute Apgar score was > or = 7 in all infants. This study suggests that leucocytosis is a non-specific response of the fetus to labour, whereas erythroblastosis reflects fetal tissue hypoxia.

The prevention of bone loss in young women treated with GnRH analogues with "add-back" estrogen therapy.

OBJECTIVE: To determine whether the addition of a low dose of oral estrogen replacement therapy (ERT) taken daily can prevent the bone loss associated with continuous GnRH analogue use. METHODS: In a double-blind, placebo-controlled study, 60 women aged 21-45 years were randomized to one of three treatment groups: placebo implant every 4 weeks plus placebo ERT tablets daily, Zoladex (goserelin 3.6 mg) implant every 4 weeks plus placebo ERT tablets daily, or Zoladex (3.6 mg) implant every 4 weeks plus estradiol valerate, 2 mg/day, with norethisterone 5 mg from days 22-28. A dual x-ray bone density scan was performed before treatment and again after six treatment cycles. The percentage bone change with respect to the initial bone density was calculated. RESULTS: There was a significant loss of bone density at both the lumbar spine and proximal femur in the group receiving Zoladex plus placebo after 6 months compared with both pre-treatment values and with the group receiving placebo plus placebo. The addition of estrogen "add-back" therapy to GnRH analogue treatment (Zoladex plus ERT) resulted in no significant change in bone density compared with either pre-treatment values or the group receiving placebo plus placebo. The study had a dropout rate of 32%. CONCLUSION: The addition of "add-back" estrogen therapy to continuous GnRH analogue use can prevent bone loss.

Analysis of L-alanine:2-oxoglutarate aminotransferase isozymes in maize.

Isozyme analysis of L-alanine:2-oxoglutarate aminotransferase (ALT) in maize indicates that there are three genes encoding this enzyme activity. Two of the gene products interact with each other to form heterodimers, while the third gene product does not interact with the other two. Another isozyme that appears after gel electrophoresis and ALT staining is shown to be glutamate dehydrogenase-1. Anaerobic treatment does not result in increased ALT levels, indicating that the previously reported increase in alanine levels caused by this treatment may be due to increases in the level of pyruvate, a substrate of ALT.

The premenstrual syndrome.

The recognition of the relationship between premenstrual syndrome and cyclical ovarian activity has enabled the rationalization of treatment. Placebo-controlled studies have established the efficacy of treatments that alter ovarian function, therefore it should no longer be necessary to rely on the placebo effect of unproven treatments such as progesterone.

The long-term effects of estradiol implant therapy for the treatment of premenstrual syndrome.

Fifty patients receiving estradiol implants for long-term treatment of premenstrual syndrome were studied over 5.6 years (range 2-8 years). There was a continued beneficial response to treatment in all symptoms, varying between 74% for bloating and 96% for depression. Menstrual cycle control improved in 31 patients and periods were less painful in 30 patients. Cyclical progestogenic symptoms occurred in 58% of patients. These were partially relieved by alterations in dose, type and duration of progestogen treatment but in 7 patients the symptoms remained severe. Eight patients had a hysterectomy during treatment; 5 for continuing progestogenic symptoms, 1 for prolapse and 2 for prolonged menstrual bleeding despite adequate progestogen therapy. Attempts to reduce the dose of progestogen led to cystic hyperplasia in 4 patients. This was treated by hysterectomy in 2 patients and corrected with two 21-day courses of progestogen in the other 2. Uterine enlargement with a mean weight of 133 g (125-145 g) associated with myometrial hypertrophy occurred in all 8 hysterectomy patients. There were no complications form venous thrombosis, pulmonary embolus, breast disease or atypical endometrial hyperplasia.

Treatment of severe premenstrual syndrome with oestradiol patches and cyclical oral norethisterone.

40 patients with premenstrual symptoms were randomly allocated to receive placebo patches or active treatment with transdermal oestradiol patches (2 x 100 micrograms) to suppress ovulation. Norethisterone 5 mg was given in each group from day 19-26 of the cycle to ensure a regular withdrawal bleed. Treatment was for 6 months with crossover at 3 months. Patients completed the Moos menstrual distress questionnaire (MDQ) and the premenstrual distress questionnaire (PDQ) daily throughout the study. 5 patients withdrew, 4 because of skin reactions and 1 because of considerable improvement with initial (active) treatment. After 3 months, both groups showed improvement in MDQ and PDQ scores. In general, between 3 and 6 months, patients who switched from active treatment to placebo had deteriorating scores while patients who switched from placebo to active treatment maintained or improved upon their initial gains. Significant improvements occurred after changing to active treatment in five of six negative MDQ symptom clusters and in six of ten PDQ symptoms.