The climacteric: blood, sweat and tears? : population based studies of well-being, attitudes and hormone replacement therapy among 1947 women aged 45-60 years

During the premenopausal years the cyclical events gradually decrease until postmenopausal amenorrhea is established. The primary process takes place in the ovaries as a gradual decline and final cessation of the generative and endocrine functions, although a certain non-cyclical endocrine activity of the ovaries is maintained until advanced age. Alexander found that the absence of ovarian steroids does not influence the hypothalamic secretion of gonadotropin releasing hormone (GnRH): the mean level of GnRH does not change with advanCing age. The lack of response of postmenopausal ovaries to endogenous gonadotropin stimulation is a result of primary age-related changes in the ovaries, not in the hypothalamus. As a result ofthe decrease in estrogens, the feed-back of ovarian estrogens on the hypothalamus diminishes, resulting in high FSH levels. A high serum FSH level is the only constant laboratory finding in the postmenopausal years. Apart from hormonal changes other effects of the aging do occur. No study so far has pointed out that in the climacteric years there is an acceleration of aging

Determinants of first prescription of hormone replacement therapy. A follow-up study among 1689 women aged 45-60 years

The aim of the present study was to ascertain the cumulative incidence of first hormone replacement therapy (HRT) and the factors that predict its prescription. In a general population 1689 women were followed for 9 months in order to trace first HRT prescriptions. Determinants (well-being, attitude towards menopause, menopausal status and another 9 variables) were measured by means of a questionnaire. Data analyses were performed for all women and for women with or without typical climacteric complaints. The cumulative 9 month incidence of HRT was 6.2%. For women without typical complaints a lower level of well-being (odds ratio 5.5; 95% Cl 1.9–15.5) and the former use of the contraceptive pill (odds ratio 4.6; 95% CI 1.0–20.5) were independently associated with HRT prescription. For women with typical complaints a positive attitude towards ‘menopause should be treated' (odds ratio 3.8; 95% Cl 1.8–8.0) was a determinant of HRT prescription. The cumulative incidence of HRT prescription is high, but from additional data it is apparent that within a period of 1 year and 9 months the majority of women stop taking HRT. For women without typical complaints, physicians prescribe HRT five times more often to those with a lower level of well-being. For women with typical complaints the physician's prescription is primarily related to the woman's attitude towards (medical) treatment of the menopause

Vasomotor symptoms and well-being in the climacteric years

Objectives: To determine more closely the relationship between vasomotor symptoms, well-being and climacteric status according to the last menstrual bleeding and according to the women themselves. Methods: A population-based cross-sectional study was executed using a postal questionnaire. Well-being of women with and without vasomotor symptoms was compared, for the different menopausal statuses. All 2729 women living in a commuter suburb of Rotterdam aged 45-60 years were approached of whom 1947 (71.3%) responded. Well-being was measured by the Inventory of Subjective Health (ISH) and three subscales of the Sickness Impact Profile (SIP). Results: The results showed that the relationship between vasomotor symptoms and well-being was dependent on climacteric status. Pre- and (middle and late) postmenopausal women with vasomotor symptoms more often experienced a relatively lower level of well- being compared to women without these symptoms. However, when the prevalence of vasomotor symptoms is as its peak, i.e. in late perimenopause, a difference in the level of well-being between women with and without vasomotor symptoms was absent. Conclusions: It is concluded that well-being and vasomotor symptoms were inversely related in all menopausal statuses except for the (late) perimenopausal phase. For this no somatic explanation seems plausible. A more social scientific explanation is suggested

Duration of hormonal replacement therapy in general practice; a follow- up study

Objectives: To assess the mean duration of use of HRT in general practice and to identify determinants of the duration of HRT use. Methods: A general population of 1689 women aged 45-60 years and enlisted in five group practices of general practitioners were followed for 9 months to trace first HRT prescriptions. All 103 women who were prescribed HRT were followed for a period of 2.25 years. Duration of HRT was assessed by using the data provided on the dispensing of HRT. Possible determinants of duration of use, such as attitude towards menopause, menopausal status and another six variables were measured by means of a questionnaire. Results: None of the 103 women received HRT for a preventive purpose; the main indication was menopausal complaints. More than 60% of the women stopped their HRT within 6 months and only 8% of the women remained on HRT for more than 2 years. The mean duration of use was 7 months. Determinants that significantly predicted the duration of HRT use were age, attitude towards treatment of the menopause and the group practice. Conclusions: The mean duration of HRT use is very short, despite the fact that the most prevalent indication is the alleviation of menopausal symptoms. Apparently, Dutch women are presently unwilling to take HRT for longer periods

Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

<p>Abstract</p> <p>Background</p> <p>Injurious mechanical ventilation (MV) may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis.</p> <p>Methods</p> <p>Normal rats and intraperitoneal (i.p.) lipopolysaccharide (LPS)-treated rats were ventilated with low (6 ml/kg) and high (19 ml/kg) tidal volumes (Vt) under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP), central venous pressure (CVP), cardiac output (CO) and pulmonary plateau pressure (P_plat) were measured. <it>Ex vivo </it>myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM)-1 and edema were measured to evaluate endothelial inflammation and leakage.</p> <p>Results</p> <p>MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function <it>ex vivo </it>but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters <it>ex vivo</it>.</p> <p>Conclusion</p> <p>MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.</p

Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway

Introduction: Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite.Methods: Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clearance measurement. Arcuate renal arteries were isolated for vasoreactivity experiment and kidneys snap frozen for staining.Results: High tidal volume ventilation resulted in lung injury, hypotension, renal hypoperfusion and impaired renal endothelium-dependent vasodilation, associated with renal dysfunction and tissue changes (leukocyte accumulation and increased expression of neutrophil gelatinase-associated lipocalin). Both WW85 and PJ-34 treatments attenuated lung injury, preserved blood pressure, attenuated renal endothelial dysfunction and maintained renal blood flow. In multivariable analysis, renal blood flow improvement was, independently from each other, associated with both maintained blood pressure and endothelium-dependent vasodilation by drug treatment. Finally, drug treatment improved renal function and reduced tissue changes.Conclusions: The peroxynitrite-induced PARP activation is involved in renal hypoperfusion, impaired endothelium-dependent vasodilation and resultant dysfunction, and injury, in a model of lung injury