RENAL FUNCTION DIFFERENCE IN PRE MENOPAUSAL AND POST MENOPAUSAL WOMEN
Postmenopausal women have an increased risk of adverse cardiovascular (CV) events. Similarly, chronic kidney disease (CKD) is a well established risk factor for CV disease and mortality.
Design We evaluated the effect of renal function on the risk of death and CV events in 1500 Nigerian pre-menopausal and postmenopausal women.
In Methods and results Renal function was estimated (e) by glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease equation. We classified postmenopausal women in two groups of e-GFR (ml/min per 1.73 m2): Z 60 (group 1) and less than 60 (group 2). The primary endpoint was major adverse CV events (MACE). The secondary endpoints were total events (MACE + death from any cause), coronary events, and stroke. During the follow-up (mean = 72.6 months), there were 200 new CV morbid events. The rate of MACE (per 100 patient-years) was 1.88 and 2.98 in the two groups of e-GFR (P < 0.0001). On univariate analysis, the incident risk of CV events was inversely related with the e-GFR values; similarly, in multiple Cox regression model, only the e-GFR maintained an independent association with MACE and secondary end-points.
For the first time, we demonstrated that the reduction of e-GFR was associated with the increased risk of death and CV events, independently of traditional CV risk factors, menopause duration, and presence of metabolic syndrome. Eur J Cardiovasc Prev Rehabil 16:481–486c 2009 The European Society of Cardiology
CHAPTER ONE
1.0 INTRODUCTION
Menopause is a stage in life when a woman stops having her monthly period. It is a normal part of aging and marks the end of a woman's reproductive years. Menopause typically occurs in a woman's late 40s to early 50s. However, women who have their ovaries surgically removed undergo "sudden" menopause. Natural menopause is the permanent ending of menstruation that is not brought on by any type of medical treatment. For women undergoing natural menopause, the process is gradual and is described in three stages, that is: Pre-menopause and Post-menopause.
Pre-menopause can begin 8 to 10 years before menopause, when the ovaries gradually produce less estrogen. It usually starts in a woman's 40s, but can start in the 30s as well. Pri-menopause lasts up until menopause, the point when the ovaries stop releasing eggs. In the last 1-2 years of pre-menopause, the drop in estrogen accelerates. At this stage, many women can experience menopause symptoms. Women are still having menstrual cycles during this time, and can get pregnant.
Post-menopause are the years after menopause. During this stage, menopausal symptoms, such as hot flashes, can ease for many women. But, as a result of a lower level of estrogen, postmenopausal women are at increased risk for a number of health conditions, such as osteoporosis and heart disease. Medication, such as hormone therapy and/or healthy lifestyle changes, may reduce the risk of some of these conditions. Since every woman's risk is different, talk to your doctor to learn what steps you can take to reduce your individual risk.
However, in this work, we are focusing on the pre-menopause and post-menopause discussing how the system functions varies in these two type of menopause.
1.2 BACKGROUND OF THE STUDY
Menopause is defined as the permanent cessation of menses as a consequence of the loss of ovarian follicular function or of surgical removal of ovaries [1]. During this period many psychological, physiological, and pathological modifications occur; in particular, cardiovascular disease (CVD) is the leading cause of death among postmenopausal women in developed countries [2]. Premenopausal women are largely protected by endogenous estrogen from CVD when compared with women of postmenopausal [3–5].
However, this ‘female advantage’ progressively decreases during the postmenopausal period, therefore by the sixth decade the women cardiovascular risk results to be similar to women of postmenopausal.
Chronic kidney disease (CKD) is associated with a significant increase in all-cause mortality [6,7] attributable, at least in part, to shared cardiovascular risk factors such as hypertension, lipid abnormalities, diabetes, obesity, and smoking [8,9].
Risk excess for CVD was also demonstrated in subjects with mild to moderate CKD [7,10], therefore the diagnosis of renal dysfunction should alert the practitioner to correctly define the total burden of CVD. Despite this association, the burden of cardiovascular risk is often not optimized, because screening for CKD is frequently limited to a measurement of serum creatinine, which does not accurately reflect glomerular filtration rate (GFR), the best indicator of renal function in healthy and diseased subjects [11].
To our knowledge, a lack of informations exists regarding that, whether CKD independently increases CVD risk qin postmenopausal women. Thus, using measure of estimated (e)-GFR, we evaluated the effect of the severity of kidney dysfunction on the risk of death and CVD events in a very large cohort Nigerian postmenopausal women.
1.3 OBJECTIVE OF THE STUDY
Little is known about the natural history of hypoactive sexual desire disorder (HSDD). We examined the sociodemographic, relationship, help seeking, sexual function, and medical characteristics of women with a clinical diagnosis of generalized, acquired HSDD by menopause status – pre-menopause and post-menopause.
1.4 PROBLEMS AND LIMITATIONS OF THE STUDY
The strength of this work is that the study population represents a large and carefully selected overall post- menopausal women. Moreover, the exclusion of women with diabetes, a very important condition in the patho- genesis of renal damage, is another strength of our study because, according to the current guidelines, diabetes is already considered a CVD risk equivalent [27].
In contrast, some limitations are present. All participants to the study are Nigerian, suggesting that our results probably cannot be extended to other populations. Our definition of e-GFR is limited to a single measurement of serum creatinine level in one determination. The fact that we did not systematically test proteinuria represent an additional limitation.
1.5 SIGNIFICANCE OF THE STUDY
Renal function assessment acquires an important clinical significance for the stratification of the global cardio- vascular risk [20]. Present findings also demonstrate that the risk of adverse events significantly increases in the lower group of e-GFR, rising to 56.5% for MACE, to 58.2% for total events, and to 62.2% for coronary events.
1.6 SCOPE OF THE STUDY
The prevalence of cardiovascular risk factors in our population is similar to that recently reported in the Framingham Heart Study [24], confirming that the association among CKD and cardiovascular risk factors is more frequent in general population even if under- estimated for post-menopause and pre-menopause.
The mean age of women with CKD Stage 5 suggests that the majority of these women are postmenopausal. Different patterns of abnormalities may be seen in women with CKD before and after menopause. The primary hormonal defect observed in premenopausal women with CKD is due to hypothalamic dysfunction. In women of reproductive age and normal renal function, a sustained midcycle increase in estradiol causes an increase in hypothalamic secretion of gonadotropin-releasing hormone (GnRH). This hormone then stimulates the pituitary gland to increase leutinizing hormone (LH) secretion and, with an increase in progesterone and estradiol, follicle-stimulating hormone (FSH) levels increase. This hormonal pattern leads to normal ovulation and menstruation. In the majority of premenopausal uremic women, the positive feedback mechanism of estradiol on the hypothalamus is blunted. The midcycle increase of progesterone, LH, and FSH is impaired, and anovulatory menstrual patterns predominate. Estradiol levels in uremic women are comparable to normal in the follicular phase, but a reduced midcycle peak has been documented. Hyperprolactinemia is present in approximately 70% of women with CKD due to reduced renal clearance, increased secretion by the anterior pituitary, and anterior pituitary resistance due to the downregulatory effects of dopamine. Menopause occurs at a younger age among women with CKD; the median age of menopause is 50–51 years in normal women and 47 years among women with CKD.
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