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Raloxifene: a review of its use in postmenopausal osteoporosis.

UNLABELLED: Raloxifene is a selective estrogen receptor modulator that partially mimics the effects of estrogens in bone and the cardiovascular system, while functioning as an antiestrogen in endometrial and breast tissue. In randomised placebo-controlled studies involving postmenopausal women or patients with osteoporosis, raloxifene 60 to 150 mg/day was effective in increasing bone mineral density (BMD) over 12- to 36-month periods. At the 60 mg/day recommended dosage, increases of 1.6 to 3.4%, 0.9 to 2.3% and 1.0 to 1.6% were reported in lumbar spine, femoral neck and total hip, respectively, versus < or =0.5% with placebo. Raloxifene 60 or 120 mg/day decreased the risk of vertebral fractures over a 36-month period in postmenopausal patients with osteoporosis. Significant reductions in radiographic fracture risk versus placebo (30 and 50%) occurred regardless of whether patients had existing fractures at baseline. Although raloxifene did not affect the overall incidence of nonvertebral fractures, a reduction in the incidence of ankle fracture was reported in comparison with placebo. In postmenopausal women, raloxifene 60 mg/day significantly reduced serum levels of total and low density lipoprotein cholesterol from baseline, compared with placebo. High density lipoprotein cholesterol and triglyceride levels were unaffected. Raloxifene 60 or 120 mg/day reduced the risk of invasive breast cancer by 76% during a median of 40 months' follow-up in postmenopausal patients with osteoporosis and no history of breast cancer. A relative risk reduction of 90% was reported for estrogen-receptor positive invasive breast cancers; estrogen-receptor negative cancer risk was unaffected by raloxifene. Raloxifene was generally well tolerated in clinical trials at dosages up to 150 mg/day. Adverse events thought to be related to raloxifene treatment were hot flushes and leg cramps. Venous thromboembolism was the only serious adverse event thought to be related to raloxifene treatment and a relative risk of 3.1 compared with placebo treatment was reported in patients with osteoporosis. Vaginal bleeding occurred in < or =6.4% of raloxifene-treated women but was reported by 50 to 88% of those receiving estrogens or hormone replacement therapy (HRT). Raloxifene treatment was not associated with stimulatory effects on the endometrium. CONCLUSIONS: Raloxifene significantly increases BMD in postmenopausal women and reduces vertebral fracture risk in patients with osteoporosis. In clinical trials, raloxifene was generally well tolerated compared with placebo and HRT, although its propensity to cause hot flushes precludes use in women with vasomotor symptoms. In particular, the lack of stimulatory effects on the endometrium and the reduction in invasive breast cancer incidence indicate raloxifene as an attractive alternative to HRT for the management of postmenopausal osteonorosis.

Bone Remodeling↗

Spotlight on estradiol and norgestimate as hormone replacement therapy in postmenopausal women.

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronized, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronized, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomized, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomized, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomized, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhea, edema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favorable uterine bleeding profile that improved over time. In a randomized trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomized studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favorable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.

Contraceptives, Oral, Synthetic↗

[Effect of postmenopausal hormone substitution on the lipid profile and coagulation factors in female smokers].

Postmenopause and smoking impair lipid profile, induce hypercoagulability and reduce fibrinolytic capacity [1, 2]. Postmenopause induced lipid changes can be reversed by oestrogen replacement [3]. Oestrogens also reduce fibrinogen level [4] and have beneficial effects on endothelium [5]. Although several studies showed that hormone replacement therapy may increase the risk of thromboembolic diseases, procoagulant oestrogen activity has not clearly been demonstrated. It is well known that smoking accelerates oestrogen metabolism [6, 7], which may attenuate its beneficial effects. The present study was undertaken to determine if there is difference in beneficial effects of oestrogens between smokers and non-smokers in terms of coagulation process and lipids. The examination was a longitudinal, one-year, before/after therapeutic study, which included healthy postmenopausal women (FSH levels at least 40 U/l), 30 smokers and 32 non-smokers who were under 55 years of age and postmenopausal period shorter than 5 years. Women with surgically induced menopause received unopposed oral oestrogens, while those with spontaneous menopause were treated with combined oral oestrogen/progestogen therapy. Before entering the study and in three-months intervals total LDL, HDL cholesterol, triglycerides and VLDL were determined, as well as plasma fibrinogen, prothrombin time, and activated partial thromboplastin time. Neither beneficial nor adverse effects of oestrogens on lipids and coagulation were observed during one-year follow-up in smokers, although subjects with longer smoking history had higher triglycerides levels after 12 months of therapy. On the contrary, oestrogen replacement reduced total and LDL cholesterol, and increased HDL cholesterol in non-smokers, with no change in triglycerides and VLDL level. A decrease in fibrinogen levels and coagulation activity, expressed by prothrombin time and partial thromboplastin time, were also observed in hormone replacement therapy in postmenopausal women who did not smoke. Peroral hormone replacement therapy does not induce favorable lipid changes in smokers. Higher triglycerides levels observed after one-year therapy in women with a longer smoking history indicate that transdermal replacement maybe more suitable in this group. Peroral oestrogen replacement has no anticoagulant or procoagulant activity in smokers during the early postmenopausal period.

Blood Coagulation↗

[Influence of hormone replacement therapy in postmenopausal women with type 2 diabetes and hyperlipidemia on lipid and glucose metabolism].

INTRODUCTION: Hormone replacement therapy (HRT) is less frequently prescribed to postmenopausal women with diabetes type 2 who have poor lipid status despite well known favorable effect of HRT on lipid levels. OBJECTIVE: The aim of this study was to assess the effect of oral HRT in postmenopausal women with type 2 diabetes and hyperlipidemia. METHOD: Continuously combined HRT, estradiol 2mg + norethisterone acetate 1mg was given to 30 women with diabetes type 2 and hyperlipidemia and two control groups of postmenopausal women (30 with hyperlipidemia only and 30 healthy women) over a 6-month period. Total cholesterol (t-HOL), triglycerides, LDL-cholesterol, HDL-cholesterol, glycosylated hemoglobin A1c (HbA1c) were evaluated in 3-month intervals. Fasting and postprandial glucose levels were evaluated monthly. RESULTS: HRT significantly decreased levels of t-HOL (X2(Friedman) = 11.712; p<0.01) and LDL-c (X2(Friedman) = 10.403; p<0.01) in postmenopausal women with type 2 diabetes. However, the effect was more pronounced in two control groups. Triglycerides (X2(Friedman) = 5.400; p > or = 0.05) and HDL-c (X2(Friedman) = 1.113; p>0.05) did not change in postmenopausal women with type 2 diabetes. Six month of oral HRT significantly decreased HbAlc (F=44.693; p<0.01). Fasting and postprandial glycemia was decreased but not significantly (X2Friedman=6.527; p>0.05). CONCLUSION: Six-month application of HRT is effective in lowering the lipid levels and HbA1c in postmenopausal women with type 2 diabetes. However, target lipid levels were not achieved.

Diabetes Mellitus, Type 2↗

Transvaginal sonographic measurements of postmenopausal ovarian volume as a possible detection of ovarian neoplasia.

BACKGROUND: The purpose of our study was to determine whether ovarian volume, as measured by transvaginal ultrasound and plotted on the nomogram of normal postmenopausal ovarian volume, could assist in the diagnosis of ovarian neoplasia. METHODS: A retrospective study was undertaken, in which the ovaries of 85 postmenopausal women were examined by transvaginal ultrasonography prior to laparotomy. Three dimensions of each ovary were measured and ovarian volume was calculated. The results were plotted on the nomogram of normal postmenopausal ovarian volume. RESULTS: Eighty-five ovarian tumors were diagnosed. The range of the mean ovarian volume varied between 98.15 cm3 to 161.81 cm3 from perimenopausal age to > 15 postmenopausal years, as compared to 2.2 +/- 1.4 - 8.6 +/- 2.8 cm in the normal postmenopausal women. The deviation from the normal volume was more striking in the malignant tumors group (100%) than in the benign group (86%). When plotted on the nomogram, these values showed significant deviation (above 2 s.d.) from the norm for each group of neoplasms in every menopausal age. CONCLUSIONS: Sonographic detection of abnormal postmenopausal ovarian volume and the demonstration of the deviation from the ovarian volume nomogram, could assist the physician in early diagnosis of ovarian neoplasia. Ovarian volume measurements can serve as the primary method leading to diagnosis of ovarian cancer.

Age Factors↗

Is postmenopausal osteoporosis related to pineal gland functions?

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

Aged↗

Concurrent use of simvastatin and estrogen--progestin therapy compared with each therapy alone for hypercholesterolemia in postmenopausal women.

OBJECTIVE: Substantial improvements in lipoprotein-lipid profiles have previously been shown with both simvastatin and combined estrogen-progestin therapy in postmenopausal hypercholesterolemic women. Since little is known about the impact of the concomitant use of these therapies, the effects of concurrent hormone therapy and simvastatin in hypercholesterolemic postmenopausal women have been evaluated. METHODS: Twenty-three postmenopausal women with fasting serum total cholesterol levels greater than 250 mg/dl received, in a randomized cross-over design, simvastatin (10 mg daily) for 8 weeks or postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens plus 5 mg of medroxyprogesterone acetate daily) for 8 weeks, with an 8-week wash-out interval between the two treatment periods. In a third, non-randomized treatment period after a second wash-out interval, each woman received a combination of simvastatin and postmenopausal hormone therapy in the same dosage regimens as above. Fasting blood was sampled monthly from baseline to measure total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides and lipoprotein(a). RESULTS: For total cholesterol, the mean decreases with hormone therapy, simvastatin and combination therapy were 12% (95% confidence interval 6-17%), 26% (20-31%) and 28% (24-31%), respectively, and for LDL cholesterol 21% (14-27%), 37% (30-44%) and 46% (41-51%), respectively. Simvastatin was more effective than hormone therapy (p < 0.001), while the effect of the combined therapy was even greater (total cholesterol, p = 0.012; LDL cholesterol, p < 0.001). The level of HDL cholesterol increased similarly with each treatment: 4% (-3-11%), 6% (2-10%) and 7% (2-13%), respectively. Triglyceride levels increased with hormone therapy and decreased with simvastatin (p < 0.001), while there was little change with the combination (effect of combined therapy vs. simvastatin, p = 0.002; vs. hormone therapy, p < 0.001). Both hormone therapy and combined therapy reduced lipoprotein(a) similarly (-23% and -14%, respectively, p = 0.078). Simvastatin had no effect on lipoprotein(a) levels. CONCLUSION: For postmenopausal women with hypercholesterolemia, use of a statin in combination with continuous combined oral estrogen and progestin therapy can result in a more cardioprotective lipoprotein-lipid profile than that achieved with either therapy used alone.

Anticholesteremic Agents↗

[Retrospective study of the relationship of height difference and bone density of postmenopausal women].

OBJECTIVE: To analyze the relationship of the height difference and bone density (BD) of premenopausal and postmenopausal women. METHODS: The height values of 191 premenopausal and postmenopausal women were recorded, and the BD values of lumbar vertebrae and hip were detected by double energy X-ray BD detector. RESULTS: The lower the height of the postmenopausal women, the less the BD value. The BD of lumbar vertebrae dropped 0.025 5 g/cm(2) with each 2 cm of the shortened height, and the BD of hip joint dropped 0.029 2 g/cm(2). The shortened value in postmenopausal women with osteoporosis was statistically greater than that in postmenopausal women without osteoporosis. CONCLUSION: The BD of the postmenopausal women can be estimated by the calculation of their shortened height value.

Aged↗

Effect of long-term hormone replacement therapy on coronary endothelial function in postmenopausal women.

OBJECTIVES: To determine the difference in endothelial function between premenopausal and postmenopausal women and to determine whether hormone replacement therapy (HRT) is associated with an improvement in coronary endothelial function. PATIENTS AND METHODS: Women undergoing coronary physiology studies for chest pain at the Mayo Clinic In Rochester, Minn, between December 1992 and April 2002 underwent assessment of coronary endothelium-independent and -dependent function with intracoronary administration of adenosine and acetylcholine, respectively. The coronary diameters, coronary blood flows, and coronary velocity reserves were measured. RESULTS: A total of 270 women (89 premenopausal and 181 postmenopausal) participated in the study. Endothelium-dependent coronary blood flow change (baseline to peak flow) in response to acetylcholine (10(-4), 10(-5), and 10(-4) mol/L) was lower in postmenopausal women compared with premenopausal women (39.7% vs 72.9%, P = .03). There was no significant difference between the postmenopausal women receiving and not receiving HRT with regard to percent change in coronary diameter (-21.8% vs -13.9%, P = .15), percent change in coronary blood flow (37.3% vs 42.7%, P = .74), or coronary velocity reserve (2.7 vs 2.7, P = .82). CONCLUSION: This study shows that the postmenopausal state is associated with a greater abnormality in coronary endothelial function at the level of the microcirculation. Moreover, HRT status was not associated with an improvement in coronary endothelial function in postmenopausal women.

Acetylcholine↗

Evaluation of the nutritional status and tumor characteristics in premenopausal and postmenopausal breast cancer patients.

Evaluation of the nutritional status, fat tissue distribution, and tumor characteristics was carried out in patients with primary breast cancer. The patients were classified into two groups according to their menopause: premenopausal and postmenopausal. Breast cancer prevalence was considerably higher in postmenopausal patients (61%). The patients' nutritional status was shown through the body mass index. Based on this indicator, the patients were characterized as nonobese and obese. In the premenopausal group, there was no significant difference between these categories, whereas the number of obese patients was significantly higher (80%) in the postmenopausal group. The analysis of tumor parameters as related to menopause and body size did not yield any significant differences. However, the estrogen receptor content was significantly higher in postmenopausal patients (p < 0.0001). Distribution of fat tissue of the android type was higher in obese postmenopausal women than in premenopausal ones (77%). The investigation showed that the breast cancer incidence odds are 3.5 times higher in obese postmenopausal than in premenopausal patients.

Adult↗

The North American Menopause Society 1998 Menopause Survey. Part I: Postmenopausal women's perceptions about menopause and midlife.

OBJECTIVE: To collect information relevant to the mission of The North American Menopause Society (NAMS)--i.e., increasing understanding of menopause--by assessing perceptions held by postmenopausal women in the United States aged 50 to 65 years regarding their menopause transition and early postmenopausal years. DESIGN: During the period from June to July 1998, The Gallup Organization conducted 752 telephone interviews with a randomly selected sample of postmenopausal women aged 50 to 65 years from across the United States, based on questions developed by NAMS. In Part I of this survey, women were asked about their personal experiences with menopause, their health-related lifestyle changes since premenopause, their frequency of discussing menopause, and their rating of preparedness for menopause. Part II of this survey, including use of hormone replacement therapy as well as use of healthcare services, will be reported in a future communication from NAMS. RESULTS: The majority (51%) of the postmenopausal women surveyed reported being happiest and most fulfilled between the ages of 50 to 65 years, compared with when they were in their 20s (10%), 30s (17%), or 40s (16%). Many areas of their lives had improved since menopause, including family/home life, sense of personal fulfillment, ability to focus on hobbies or other interests, relationship with spouse/partner, and friendships. A majority (51%) said their sexual relationships had remained unchanged. Approximately three-quarters of women surveyed reported making some type of health-related lifestyle change, such as stopping smoking, at menopause/midlife. Women who had undergone hysterectomy expressed more improvement than women with an intact uterus, especially in the areas of sexual relationships, spouse/partner relationships, personal fulfillment, and physical health; data are not available regarding the health state of these women before surgery or whether they experienced surgical menopause, but this improvement did not appear to be the result of hormone replacement therapy. Women tended to look to women from their own generation for menopause-related information and believed that they have prepared the younger generation for menopause better than they were prepared by their mothers' generation. Those surveyed advised younger women to engage in healthful activities and become knowledgeable so that they could make informed health decisions. CONCLUSIONS: Although the postmenopausal women surveyed had differing views of menopause as well as their perceptions of postmenopause compared with premenopause, the majority viewed menopause and midlife as the beginning of many positive changes in their lives and health. Hysterectomy was a factor associated with improved sexual relationships, spouse/partner relationships, sense of personal fulfillment, and physical health.

Adaptation, Physiological↗

[Cytokines of bone turnover in postmenopause and old age].

BACKGROUND: The aim of the study was the assessment of the influence of cytokines on bone ageing by measuring their level in serum and their secretion in vitro by monocytes from women of different age. METHODS: The levels of cytokines in 34 postmenopausal subjects and 14 old subjects were compared to those measured in 13 cycling subjects who were considered as control group. Subjects suffering from diseases inducing secondary osteoporosis, subjects taking medications that affect bone metabolism and alcohol- or tobacco-consumers were excluded from the study. The levels in serum of (i) the bone stimulating peptide insulin-like growth factor-I (IGF-I), (ii) the inhibitor of bone resorption interferon-gamma (IFN gamma), (iii) the stimulators of bone resorption interleukin-1 beta (IL-1 beta) tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) were evaluated by immunoassay. IL-1 beta, TNF alpha and IL-6 secreted by monocytes (MO) cultured in vitro from peripheral blood of the same subjects were measured, too. Bacterial endotoxin (LPS) was used as stimulator for cytokine secretion by monocytes. RESULTS: Unlike IFN gamma, which was unaltered, circulating IGF-I level was found significantly diminished in postmenopausal and old subjects compared to control group. Among stimulators of bone resorption, IL-6 was greatly increased in postmenopausal and old subjects, while TNF alpha was reduced in postmenopausal group. In the supernatants of unstimulated monocytes the level of IL-1 beta was consistently decreased in old subjects; TNF alpha was found to be decreased in postmenopausal and old subjects. The stimulation index (SI), calculated as the ratio between the level of cytokines secreted by LPS-stimulated MO and the level of cytokines secreted by unstimulated MO, was found to be significantly increased for IL-1 beta and TNF alpha in postmenopausal subjects vs control group. In the old subjects the SI for IL-6 was enhanced. CONCLUSIONS: The data collected suggest that the measurement of cytokines in serum and supernatants from monocytes may give a picture of the mechanisms regulating bone aging.

Adult↗

Decreased libido in postmenopausal women.

As baby boomers age, the health issues of postmenopausal women have gained increasing media attention. Sexual well-being is an important health component for these women. The estimated rate of female sexual dysfunction in the United States is an astounding 25% to 63% with the most prevalent age group being postmenopausal women. Decreased libido is a major complaint of postmenopausal women, and many seek medical consultation for this problem. Unfortunately, current female sexuality research for this population is clearly deficient. Additionally, medical providers tasked with managing postmenopausal sexual dysfunction often lack training, experience, and the confidence necessary to handle sexuality concerns. Nurse practitioners, as superior counselors, are in a prime role to address this issue. The purpose of this report is to focus on the multifaceted problem of decreased libido in postmenopausal women, with management strategies to assist practitioners in managing and addressing this problem in the clinical setting. The report will investigate several physical, hormonal, and psychosocial factors impacting decreased libido in these women. Current and past research into this area will be analyzed to better define the current professional consensus on managing decreased libido in postmenopausal women.

Aged↗

[Response of gastrin after an oral calcium load in healthy women and in postmenopausal patients without hormone replacement therapy].

BACKGROUND: Gastrin has a wide variety of functions on the digestive system including the regulation of gastric acid secretion, being a growth factor for the non antral gastric mucosa and the stimulation of mucosal proliferation in the large and small intestines. Animals studies showed that various diseases of the digestive system have better clinical evolution in the presence of estrogens as is the case of peptic ulcers, now little is known in humans about this phenomenon. OBJECTIVE: To evaluate the response of gastrin after an oral calcium load in normal and postmenopausal women without hormone replacement therapy. PATIENTS AND METHODS: We studied 10 healthy women with mean age 25.3 +/- 1.79 yr (range: 23-28 yr) and 7 postmenopausal women without previous treatment and a mean age 56.5 +/- 6.4 yr (range: 50-70 yr). A permeable vein with physiologic solution was obtained in order to maintain a permeable vein in the antecubital fossa to obtain blood samples for the determination of gastrin. Before an oral administration of 1 g of calcium baseline samples were taken at time 0 and thereafter on 30, 60, 90, 120, 150, and 180 minutes. Gastrin levels were determined by RIA using CIS Bio-International commercial kits. RESULTS: Basal gastrin levels were x: 72.54 +/- 15.9 pg/mLK in normal women and x: 61.1 +/- 39.62 in postmenopausal women. Basal gonadotrophins were x: 62.1 +/- 26 and x: 32.9 +/- 7.3 for FSH and LH respectively and estradiol level of x: 13.9 +/- 4.2 pg/mL. Normal volunteers had a peak secretion of x: 173.4 +/- 15 pg/mL at 90 minutes and in postmenopausal women a peak of x: 66.2 +/- 50 at 60 minutes. Comparing the magnitude of the response between the healthy volunteers and the postmenopausal women at 90 and 120 minutes the statistical significance was a (p < 0.005) and (p < 0.001), respectively. CONCLUSIONS: These results demonstrate the lack of response of gastrin levels to the calcium stimulus in postmenopausal women probably due to the lack of hormone replacement therapy. Further studies are needed to best understand the role of sexual hormones on the synthesis and secretion of gastrin in the digestive system especially the role of the estrogens.

Administration, Oral↗

Expression of messenger ribonucleic acid encoding steroidogenic enzymes in postmenopausal ovaries.

To investigate expression of steroidogenic enzymes involved in androgen and estrogen synthesis in the stroma of postmenopausal ovaries.Ovarian stromal tissue samples were obtained at hysterectomy from postmenopausal women who had hysterectomy and oophorectomy. Tissues were frozen immediately in liquid nitrogen and kept frozen until RNA was extracted. Total RNA was examined by Northern blot analysis using (32)P-labeled cDNA probes encoding human P450 side chain cleavage (P450(SSC)), P450(17alpha), and cytochrome P450 aromatase (P450(arom)). Concentrations of mRNA encoding cytochrome P450(SSC), cytochrome P450 17alpha-hydroxylase (CYP17), and P450(arom) were determined in the ovarian stroma. We detected P450(SSC) mRNA in all postmenopausal ovaries studied. P450(SSC) mRNA was increased threefold in the ovarian stroma of postmenopausal women with endometrial cancer and endometrial hyperplasia. CYP17 mRNA was detected in the ovarian stroma of all women with endometrial cancer. P450(arom) mRNA was not detected in the ovaries studied. Postmenopausal ovaries possess enzymes for initiation of steroidogenesis. Enzymes essential for androgen synthesis were expressed in the ovarian stroma of postmenopausal women with endometrial cancer or hyperplasia.

Aged↗

[Association of polymorphisms of vitamin D receptor gene start codon and 3'-end region with bone mineral density in postmenopausal women].

OBJECTIVE: To determine whether vitamin D receptor(VDR) gene start codon polymorphisms and 3'-end region polymorphisms exerted a combined influence on bone mineral density(BMD) in Han postmenopausal women in Beijing area. METHODS: The VDR Fok I and 3'-end region genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 110 unrelated postmenopausal women. BMD was measured at the lumbar spine (L(2-4)), femoral neck(Neck), Ward's triangle(Ward's) and trochanter (Troch) using duel-energy X-ray absorptiometry. RESULTS: The frequencies distribution of Fok I, Apa I, Bsm I and Taq I alleles in this cohort all followed the Hardy-Weinberg equilibrium. No significant association of Fok I, Apa I or Taq I genotype with BMD in postmenopausal women was found when these polymorphisms were considered independently, except for Bsm I genotype. When a combined analysis of VDR gene Fok I and 3'-end region polymorphisms was carried out, cross-genotyping Fok I and Apa I polymorphisms was significantly associated with BMD at the L(2-4) (P<0.001), and cross-genotype of Fok I and Taq I was also significantly associated with BMD at the Neck and Troch sites (P<0.05). However, cross-genotyping Fok I and Bsm I polymorphisms was not significantly associated with BMD. Cross-genotyping Apa I and Bsm I or Taq I polymorphisms was not associated with BMD in postmenopausal women, either. CONCLUSION: Although Fok I polymorphisms of VDR gene were not significantly associated with BMD in postmenopausal women, VDR gene Fok I and 3'-region polymorphisms (Apa I and Taq I) had a combined effect on the BMD in postmenopausal women.

3' Flanking Region↗

Vascular function of forearm microcirculation in postmenopausal women with type 2 diabetes: potential benefit of hormone replacement therapy?

OBJECTIVE: To study the potential effects of hormone replacement therapy (HRT) on vascular function of the peripheral circulation in postmenopausal women with type 2 diabetes. METHODS: Seventeen premenopausal women aged 47.4 +/- 4.4 years (PreM), 23 nondiabetic postmenopausal women aged 59.4 +/- 7.0 years (PM), 15 postmenopausal women with type 2 diabetes aged 60.3 +/- 7.2 years (PMD) and 12 postmenopausal women with type 2 diabetes using HRT aged 61.2 +/- 4.0 years (PMDHRT) were studied. Vascular function of the peripheral circulation was investigated by measuring hyperemic responses of the forearm microcirculation following an ischemic stimulus using venous occlusion, strain-gauge plethysmography. Fasting lipids, glucose and glycated hemoglobin (HbA1c) were also measured. RESULTS: Forearm vascular function was significantly impaired in the PMD group: maximal blood flow (ml/100 ml/min) was 15.23 +/- 8.19 vs. 28.21 +/- 12.30 (PreM), 23.62 +/- 6.62 (PM) and 23.37 +/- 5.78 (PMDHRT) (p = 0.004); flow debt (ml/100 ml) was 3.99 +/- 2.83 vs. 7.40 +/- 4.92 (PreM), 5.66 +/- 3.67 (PM) and 8.57 +/- 4.84 (PMDHRT) (p = 0.0018); vascular resistance (mmHg/ml/100 ml/min) was 11.90 +/- 9.02 vs. 5.04 +/- 2.41 (PreM), 5.55 +/- 2.69 (PM) and 5.96 +/- 1.88 (PMDHRT) (p = 0.003). Fasting lipids, HbA1c and body mass index were not significantly different between the two diabetic groups. CONCLUSIONS: Postmenopausal women with diabetes have abnormal vascular function of resistance arteries that may improve with HRT. HRT may therefore reduce cardiovascular risk in postmenopausal women with type 2 diabetes, and a clinical end-point trial is warranted to test this hypothesis.

Adult↗

Normal and abnormal 18F-FDG endometrial and ovarian uptake in pre- and postmenopausal patients: assessment by PET/CT.

UNLABELLED: The purpose of the study was to assess physiologic endometrial (18)F-FDG uptake during the 4 phases of the menstrual cycle and to differentiate between physiologic and malignant endometrial uptake. METHODS: Endometrial (18)F-FDG uptake, expressed as standardized uptake value (SUV), was measured on PET/CT images of 285 consecutive female patients, of whom 246 (112 premenopausal and 134 postmenopausal) had no known gynecologic malignancy and 39 (14 premenopausal and 25 postmenopausal) had cervical, endometrial, or ovarian cancer. RESULTS: Two peaks of increased endometrial (18)F-FDG uptake were identified during the 4-phase cycle. The mean SUVs were 5 +/- 3.2 and 3.7 +/- 0.9 in menstruating and ovulating patients, respectively, and 2.6 +/- 1.1 and 2.5 +/- 1.1 in patients in the proliferative and secretory phases, respectively. The mean endometrial SUV in postmenopausal patients not receiving hormonal therapy was 1.7 +/- 0.5. Oligomenorrhea and benign endometrial abnormalities were associated with increased (18)F-FDG uptake. Neither contraceptives nor hormonal therapy was associated with a significant increase in endometrial uptake. In addition to the increased tumor uptake measured in patients with cervical cancer (14.9 +/- 7.3 in postmenopausal patients and 12.2 +/- 6.6 in premenopausal patients), increased uptake was also found in the adjacent endometrium, although it appeared normal on CT (4.8 +/- 2 in premenopausal patients and 4.7 +/- 2.8 in postmenopausal patients). Increased ovarian (18)F-FDG uptake was detected in 7 patients with ovarian cancer (9.1 +/- 4) and in 21 premenopausal patients without known ovarian malignancy (5.7 +/- 1.5, P < 0.01), of whom 15 were at mid cycle and 3 reported oligomenorrhea. An ovarian SUV of 7.9 separated benign from malignant uptake with a sensitivity of 57% and a specificity of 95%. CONCLUSION: In premenopausal patients, normal endometrial uptake of (18)F-FDG changes cyclically, increasing during the ovulatory and menstrual phases. Increased uptake in the endometrium adjacent to a cervical tumor does not necessarily reflect endometrial tumor invasion. Increased ovarian uptake in postmenopausal patients is associated with malignancy, whereas increased ovarian uptake may be functional in premenopausal patients.

Endometrial Neoplasms↗