Hormone Replacement Therapy Does Not Affect the 24-Hour Heart Rate Variability in Postmenopausal Women:

Postmenopausal women are at greater risk of coronary heart disease. The results of previous studies of the effects of hormone replacement therapy (HRT) on cardiac autonomic modulation in postmenopausal women have been contradictory. This study examined whether continuous treatment for 3 months with estradiol alone (ERT) or with estradiol plus norethisterone (HRT), increases 24-hour heart rate variability (HRV) in postmenopausal women. In this double-blind, placebo-controlled trial, 40 healthy postmenopausal women, 46–63 years of age, were randomly assigned to (1) continuous 2 mg of estradiol plus 1 mg of norethisterone acetate daily (HRT, n = 13), or (2) 2 mg of estradiol daily (ERT, n = 14), or (3) placebo (n = 13). Before and after 3 months of therapy, blood estradiol concentrations were measured and 24-hour electrocardiograms recorded for evaluation of 24-hour time-domain indices of HRV, and indices derived from the three-dimensional return map. Both hormone replacement regimens significantly increased blood estradiol concentrations, while no change occurred in the placebo group. In the three treatment groups, multiple 24-hour time-domain indices of HRV and indices derived from the three-dimensional return map remained unchanged. In healthy postmenopausal women, HRT with estradiol or estradiol and norethisterone for 3 months did not modify cardiac autonomic activity evaluated by 24-hour indices of HRV. These findings are consistent with a lack of protective cardiovascular effect of HRT described in recent large randomized trials.     

Norethisterone therapy for bleeding due to gastrointestinal telangiectases in Glanzmann's thrombasthenia

We report a case of a patient with Glanzmann's thrombasthenia and anti-GPIIb/IIIa alloantibodies who developed life-threatening and intractable bleeding from gastrointestinal telangiectatic lesions. After a period of transfusion-dependent gastrointestinal bleeding despite tranexamic acid, oral iron, omeprazole and platelet transfusions, the use of oral norethisterone produced a significant improvement with a marked reduction in her transfusion requirements.     

The Danish osteoporosis prevention study (DOPS): project design and inclusion of 2000 normal perimenopausal women

Objective: In 1990 we initiated a 20 year, partly randomised study (Danish Osteoporosis Prevention Study, DOPS) in order to (a) evaluate clinical, biochemical and osteodensitometric variables as predictors of low bone mass and future osteoporotic fractures, and (b) test the hypothesis, that hormone replacement therapy (HRT) initiated shortly after menopause reduces the risk of later osteoporotic fractures. This report describes study design and baseline characteristics of the DOPS-cohort. Methods: The study design is pragmatic, attempting to mimic the normal clinical situation. Several HRT alternatives are available according to clinical need. It was considered futile, impractical and unethical to use placebo for 20 years. Instead the study focus on hard endpoints (fractures) confirmed by independent persons (peripheral fractures) or by methods which allow investigator blinding (spinal X-rays). Statistical evaluation will focus on intention to treat analyses evaluating the decision of HRT and it’s feasibility. With a compliance of 60% we will have sufficient statistical power (88%) to detect a fracture reduction of 40% in the treatments group. Clinical risk factors, current daily intakes of macronutrients, vitamins and minerals, anthropometric variables, biochemical variables (including bone markers and 25-hydroxyvitamin D), regional bone mineral density (BMD) and total body composition were assessed in all participants at entry and at various follow up intervals. Results: 2016 study participants were recruited by direct mailing to a random sample of 45–58 years old women. In the randomised arm 501 were allocated to HRT and 505 to no treatment. In the non-randomised arm 219 preferred HRT and 791 preferred no treatment. Post-randomisation analysis revealed a slight but significant difference in age (50.01 versus 50.44 years) but no difference in menopausal age, prevalence of hysterectomy, educational level, BMI, serum bone alkaline phosphatase, serum osteocalcin, urine hydroxyproline or serum 25-hydroxyvitamin D. In the non-randomised arm women preferring HRT were closer to menopause, had a higher prevalence of hysterectomy, were better educated, were leaner, and had lower bone turnover than the women, who refused HRT. Conclusion: It is possible to include a sufficient number of perimenopausal women in a randomised 20 year study on the antifracture effect of HRT.     

甲基睾丸素及其它甾体的HPLC测定

以ＨＰＬＣ法测定甲基睾丸素及其它甾体，采用Ｓｈｉｍ－Ｐａｃｋ ＯＤＳ柱，甲醇－水（７２：２８）为流动相，炔诺酮为内标，检测波长为２４１或２５４ｎｍ。与ＴＬＣ、ＵＶ法相比，本法简便、准确、可靠、重现性好。     

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Pharmacokinetics,pharmacodynamic and endometrial effects of a single dose of 200 mg norethisterone enanthate

Ovulation was confirmed by daily analyses of the peripheral plasma levels of estradiol (E₂)⁴) and progesterone (P) in a pre-treatment cycle of 14 subjects. An endometrial biopsy was taken either in the proliferative or in the secretory phase of the cycle. On the 5th day of a subsequent cycle 200 mg norethisterone enanthate (NET-EN) was administered intramuscularly. The levels of E₂, P and those of NET were analyzed during the next 19 days and again during 44–60 days following the injection. The endometrial biopsy was repeated on the 23rd and 59th day of the treated cycle. The levels of NET reached a peak of 34.3 nmol/1 on the sixth post-injection day and decreased to below detectable limits in 3 of 12 subjects by the end of the observation. Ovarian activity was completely suppressed in all women during the first period, but returned to different levels in 11 subjects during the second. Four of them exhibited ovulatory steroid pattern. The morphologic changes of the endometrium reflected the progestogen effect in the first post-injection period but were characteristic of the ovarian reaction in the second.     

A randomised, double-blind, cross-over study into the effect of sequential mestranol and norethisterone on climacteric symptoms and biochemical parameters

A randomised, double-blind, cross-over study into the effect of graded sequential mestranol and norethisterone on climacteric symptoms was performed. The study group consisted of 23 post-menopausal women who had previously undergone hysterectomy. Active therapy resulted in a significant reduction in hot flushes and night sweats. There was a slight improvement in insomnia, lack of energy and confidence but the other symptoms were not significantly altered. A small placebo effect was noted but this was only significant 1 mth after active treatment had been discontinued in the group of women receiving placebo second. Active treatment also resulted in a significant reduction in serum sodium, calcium, albumin, alkaline phosphatase and cholesterol, and increase in serum triglycerides, but no alteration in the other biochemical parameters, weight or blood pressure.     

Late (4–8 years) outcome of treatment with megadoses of fluphenazine enanthate in drug-refractory schizophrenics

Fourteen schizophrenics who did not respond to standard doses of neuroleptics have been treated with megadoses of fluphenazine enanthate during a period of 4–8 years. Repeated attempts have been made to reduce the dose to the standard dosage. Some of the patients have gradually been transferred to maintenance treatment with standard doses, with megadoses given only during psychotic relapse. The megadose treatment has led to substantial reduction in social disablement, enabling the patients, for instance, to leave the hospital or live in an open ward. These patients have been evaluated with rating scales for psychopathology and side effects, and subjected to EEG, ECG, chest X-ray, and examinations for skin and eye changes and local infiltrations. Laboratory tests, including anti-DNA examination, have also been performed. These patients, treated with high total doses of different oral neuroleptics and fluphenazine depot, showed some EEG and ECG abnormalities, eye changes, slight leucopenia, a low number of staff nuclei neutrophils and infiltrations at the injection site, but these reactions did not result in any practical handicaps. The rating scales showed dyskinetic movements, usually slight, in six out of the 14 patients studied.     

A randomized study of metabolic effects of four low-estrogen oral contraceptives: I. Results after 6 cycles

Healthy, non-smoking, normotensive, well-motivated young women were assigned at random to one of four different, commercial, low-estrogen, oral contraceptive products. Measurements of biochemical parameters were made on blood specimens collected from fasting subjects twice during the late pretreatment cycle, then again during each late treatment cycle for six months. All women assigned to one product (0.5mg NET + 35 microgram EE) dropped out of the study before the end of the fifth cycle, but discontinuations with the other three products were few. While numbers of subjects are small, the groups are closely matched and most metabolic differences are statistically significant. Products containing EDA and NET were associated with increases in serum total cholesterol and triglycerides, but decreases in HDL-cholesterol. In contrast, the LNG-containing preparation produced significantly less effect on these tests. A similar pattern was seen with a range of blood coagulation and fibrinolytic factors, Minimal alterations were seen with the LNG preparation, while those containing NET or EDA showed marked increases in factors I. VII, VIII, X and plasminogen, associated with a decrease in antithrombin III. It is suggested that differences in the metabolic impact of the various commercially available low-estrogen preparations, combined with effects on intermenstrual bleeding, allow a choice of the progestogen component most suitable for general use.