Acute psychiatric admission and menstrual cycle phase in women with schizophrenia.

The clinical observation of a possible relation between the phases of the menstrual cycle and psychotic illness dates well back to the beginning of the nineteenth century. This relation is considered to provide further evidence for the protective effect of oestrogens in schizophrenic women and is summarised by the so-called oestrogen hypothesis. In addition, the hypoestrogenism hypothesis postulates a hypofunction of the gonads in women with schizophrenia with subsequent oestrogen deficiency syndrome. The aim of the present clinical study was to answer the question whether there is a perimenstrual increase in hospital admissions of women suffering from an exacerbation of schizophrenia. Two samples of premenopausal women with schizophrenia were investigated (sample 1: n = 115; sample 2: n = 170). In both samples there was a significant increase in admissions in the perimenstrual phase - three days before and three days after the first day of the menses (sample 1: P = 0.002, sample 2: P = 0.028, binomial test). 37.4% of the patients were admitted during the perimenstrual phase of the cycle in sample 1, 31.8% in sample 2. Regarding age, age at onset, and duration of illness, no difference was found between the group admitted to hospital during the perimenstrual phase versus the group admitted during the rest of the menstrual cycle in either of the samples. The results are discussed in relation to the possibly underlying physiological mechanisms.

Reduced cerebrospinal fluid estradiol levels are associated with increased beta-amyloid levels in female patients with Alzheimer's disease.

Recent in-vitro studies indicate that estrogens such as 17beta-estradiol (E2) may decrease the production of beta-amyloid 1-42 (Abeta42), a peptide central for the formation of senile plaques in Alzheimer's disease (AD). To test this hypothesis in a clinical study, cerebrospinal fluid levels of E2 were compared between 30 female AD patients and 11 female patients with non-dementing diseases such as major depression and investigated with respect to beta-amyloid 1-40 and Abeta42 levels. E2 levels were significantly (P<0.05) lower in the AD group than in controls; within the AD group E2 levels were inversely correlated with Abeta42 concentrations (r=-0.36, P=0.05). This is the first clinical study providing evidence for an influence of E2 on Abeta42 metabolism in vivo. This observation corresponds to the putative beneficial effects of estrogen replacement therapy on the development and course of AD.

Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints.

OBJECTIVES: To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch (Fem7, Merck KGaA, Germany) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo. DESIGN: A multicentre, randomized, double-blind study with an initial screening phase (phase I), a 3-month double-blind placebo-controlled phase (phase II) and a 3-month open follow-up phase (phase III). METHODS: 186 patients were randomized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up (total duration; 6 months). The changes in Kupperman Index (primary efficacy variable), hot flushes and urogenital symptom score were studied from baseline to the end of the study. In addition, skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy. RESULTS: A reduction in Kupperman Index was observed in both groups, and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo (last value vs. baseline P = 0.0006). From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group. The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase (mean weekly hot flush reduction at the end of the placebo-controlled treatment phase: -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo, P = 0.0025). The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1-3 and 4-7. Subjective acceptance of the 7-day-Estradiol patch was good and 72.4% of patients who took active medication throughout the study were willing to consider continuing its use. CONCLUSIONS: The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women, with a rapid onset of action and 7-day duration of therapeutic effect. Although a placebo effect was observed, the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period.

Serum leptin levels and body weight in postmenopausal women under transdermal hormone replacement therapy.

Leptin, the adipocyte-specific product of the ob gene, is implicated in body weight regulation and energy balance. We investigated the influence of hormone replacement therapy (HRT) on the body mass index (BMI) and serum leptin levels in 20 postmenopausal, nonobese women treated with transdermal HRT (delivery rate 50 microg 17beta-estradiol/24 h, 1 patch per week) for 6 months. Serum leptin levels were measured by ELISA and results were compared by means of the Student's paired t-test or Pearson's correlation. The mean patient age was 55+/-6.04 years. The mean body weight prior to the start of the study was 69.39+/-9.37 kg, and the BMI before HRT was 26.92+/-4.47 kg/m2. Both parameters remained unchanged under therapy. No significant change in absolute serum leptin values (18.8+/-8.4 ng/ml; 20.47+/-9.7 ng/ml; 17.92+/-8.7 ng/ml at 0, 4 and 6 months respectively) or in adiposity-corrected values (serum leptin/BMI) (0.68+/-0.24; 0.75+/-0.29; 0.67+/-0.26 at 0, 4 and 6 months respectively) were found. Serum leptin levels correlated well with BMI (r = 0.7193, p<0.0001). There was no significant correlation of estradiol with serum leptin levels before or during therapy. In summary, low dose, transdermal HRT exhibited no influence on serum leptin levels or BMI in postmenopausal women. These data suggest that low dose HRT does not influence body weight regulation in postmenopausal women.

[Serum lipids in treatment with transdermal estradiol and oral norethisterone acetate]. / Serumlipide unter Behandlung mit transdermalem Ostradiol und oralem Norethisteronacetat.

With transdermal estradiol substitution the so called "primary liver passage" is avoided. Taking into account also the low dose of estradiol the risk of hepatic side effects can be reduced. On the other hand, it was assumed that for the same reason desirable lipid effects regarding cardiovascular protection may also not be possible, in contrast to oral estrogen treatment. Treating 26 postmenopausal women with the estradiol patch releasing 0.05 mg daily and with 1 mg oral norethisterone acetate, added at least during 10 days in each cycle, a significant reduction was observed in total cholesterol as well as in LDL- and VLDL-cholesterol of about 15-20%. HDL-cholesterol first showed a decrease and thereafter it increased again to basic level. It is supposed that the reason for this may be different effects on subfractions of HDL-cholesterol. The triglycerides were lowered to about 20%. This result is thought to be important because oral estrogens have been associated with increases in triglycerides. By lowering LDL-cholesterol as well as triglycerides, both serum lipids, most important with respect to cardiovascular protection, are shown to be influenced positively.

[Oral or transdermal estrogen substitution therapy in climacteric?]. / Orale oder transdermale Ostrogensubstitutionstherapie im Klimakterium?

There are several preparations available for hormone substitution in the postmenopause. The aim of this paper is to give a short review on oral and transdermal hormone substitution therapy. Are there different effects, side effects or metabolic interactions? Both the oral and the transdermal application are similar in reduction of menopausal symptoms. Neither vaginal cytologic differences, nor different bleeding patterns and no increase in weight or blood pressure changes can be observed with either application form. Despite a local irritation of the skin (3-7%) with transdermal oestradiol, only 4% of the patients show systemic side effects either with oral or transdermal hormone substitution. The oral administration results in higher 17 beta-oestradiol levels, higher oestrone levels and an increase in some liver proteins, possibly as a result of the first pass effect of the liver. The cardioprotective effects of oral hormone substitution are well known. Furthermore transdermal oestradiol therapy results, also in a decrease of cholesterol and atherogenic LDL-C levels. In contrast to oral oestrogens, no effect on triglycerides or its decrease can be observed; in view of conflicting results regarding HDL-C, further studies are necessary. With both applications, there are no clinically relevant alterations in thyroid, carbohydrate- or blood coagulation metabolism: Even the prevention of osteoporosis in postmenopausal women, which is establish with oral hormone therapy, can also be observed with transdermal hormone substitution.