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Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis.

PURPOSE: Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Accumulating evidence indicates that postmenopausal hormone therapy may reduce the risk of colorectal cancer in women. METHODS: Through MEDLINE computer searches (January 1966 to September 1998) and a review of references, we identified English-language articles with quantitative data on the relation of postmenopausal hormone therapy to colorectal cancer. We reviewed the studies and made summary estimates of relative risks (RR) by weighting the results of each study in proportion to its precision, using a general variance-based, fixed-effects model. RESULTS: In our meta-analysis of 18 epidemiologic studies of postmenopausal hormone therapy and colorectal cancer, we found a 20% reduction [RR = 0.80, 95% confidence interval (CI), 0.74 to 0.86] in risk of colon cancer and a 19% decrease (RR = 0.81, 95% CI, 0.72 to 0.92) in the risk of rectal cancer for postmenopausal women who had ever taken hormone therapy compared with women who never used hormones. Much of the apparent reduction in colorectal cancer was limited to current hormone users (RR = 0.66, 95% CI, 0.59 to 0.74). CONCLUSION: Observational studies suggest a reduced risk of colorectal cancer among women taking postmenopausal hormones. There is biologic evidence to support this association.

Antineoplastic Agents, Hormonal↗

Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer.

OBJECTIVE: Our purpose was to investigate the frequency of ovarian cysts in tamoxifen-treated breast cancer patients. STUDY DESIGN: The study population included 95 consecutive tamoxifen-treated premenopausal and postmenopausal women with breast cancer who were followed up by the outpatient clinic at the Hadassah University Hospital between September 1990 and June 1992. Tamoxifen was administered orally (20 mg/day). All patients underwent a pelvic examination and vaginal ultrasonography with a 5 MHz vaginal probe. RESULTS: During the study 11 of 95 tamoxifen-treated breast cancer patients (11%) had ovarian cysts. Five cysts were detected in postmenopausal women (6.3% of the postmenopausal women) and six in premenopausal women (37.5% of the premenopausal women). In postmenopausal and premenopausal women the mean tamoxifen treatment interval was 19.4 +/- 7.8 months (range 4 to 48 months) and 28 +/- 6.1 months (range 12 to 54 months), respectively (p = 0.41). In 8 of the 11 patients the ovarian cystic enlargement disappeared after cessation of tamoxifen treatment. Two patients underwent laparotomy because of persistent cysts and the third because of a rapidly growing myoma. The three cysts were found to be benign. CONCLUSION: Ovarian cysts are a common side effect of tamoxifen treatment. The ovarian cysts can develop in tamoxifen-treated premenopausal as well as postmenopausal women with breast cancer. Most of the tamoxifen-associated cysts disappear after tamoxifen treatment is abandoned.

Adult↗

Transvaginal ultrasonographic measurement of endometrial thickness in postmenopausal women receiving estrogen replacement therapy.

OBJECTIVE: This study was undertaken to evaluate endometrial thickness by transvaginal ultrasonography in asymptomatic postmenopausal women receiving estrogen replacement therapy. The endometrial thickness in this study group was compared with endometrial thickness measurements in a group of women who had abnormal postmenopausal bleeding. The recent literature was reviewed. STUDY DESIGN: Asymptomatic postmenopausal women receiving estrogen replacement, seen for routine examination during the 1-year period from Jan. 1, 1994, to Dec. 31, 1995, had the endometrium evaluated by transvaginal ultrasonography. Women with abnormal postmenopausal bleeding were likewise evaluated and their measurements compared with those of the study group. RESULTS: Twenty-seven different estrogen and estrogen-progestin combinations in 327 asymptomatic women were studied. Additionally, 24 women who were bleeding, not receiving estrogen, and 46 women with abnormal bleeding on estrogen therapy underwent ultrasonography of the endometrium. Endometrial thickness ranged from 1 to 15 mm in women on a regimen of combined estrogen-progestin therapy, 1 to 14 mm in women using sequential estrogen-progestin, and 3 to 15 mm for women receiving unopposed estrogen in the study group. For women with abnormal bleeding not using estrogen, the endometrium measured an average of 12.3 mm (range 2 to 29 mm), with unopposed estrogen 8.3 mm (range 4 to 13 mm), and for estrogen with progestin 6.5 mm (range 2 to 15 mm). Significant pathologic features were found in those women who had bleeding and endometrial measurements between 5.0 and 29 mm. CONCLUSION: There was no significant difference between endometrial thickness measurements in women receiving various combinations of estrogen replacement. In general, expected endometrial measurements can range from 1 to 15 mm. In women with postmenopausal bleeding, however, significant pathologic features may exist with an endometrium measuring as little as 5 mm.

Aged↗

Hysteroscopy in women with abnormal uterine bleeding on hormone replacement therapy: a comparison with postmenopausal bleeding.

OBJECTIVE: To determine the role of outpatient diagnostic hysteroscopy in patients with abnormal uterine bleeding (AUB) on hormone replacement therapy (HRT) and to contrast this with a control group of women presenting with postmenopausal bleeding. DESIGN: Comparative observational study. SETTING: Outpatient hysteroscopy clinic in a university hospital. PATIENTS: Three hundred ten patients undergoing outpatient hysteroscopy. INTERVENTIONS: Outpatient diagnostic hysteroscopy with endometrial biopsy when indicated. MAIN OUTCOME MEASURES: Hysteroscopic findings, need for cervical dilatation and local anaesthesia, correlation between hysteroscopy and histologic diagnosis. RESULTS: There were 157 (7.1%) patients with AUB on HRT and another 153 (6.9%) with postmenopausal bleeding out of 2,203 outpatient hysteroscopies. Hysteroscopy was successful in 97% and 92% of patients, respectively, and intrauterine pathology was diagnosed in 46.7% and 39.7% of these cases. Functional endometrium was noted significantly more often with HRT and endometrial atrophy with postmenopausal bleeding. Overall, local anesthesia was used in 126 (40.6%) and shown to be associated significantly with the need for cervical dilatation. Endometrial biopsy was attempted in 125 (80%) and 119 (78%) patients in the study and control groups, but was unsuccessful significantly more often with postmenopausal bleeding (38.7%) versus 16%). There were six cases of endometrial carcinoma, all in the control group. CONCLUSION: There is a high incidence of intrauterine abnormalities in women with menstrual symptoms while taking HRT, but the pathology differed from those with postmenopausal bleeding. As focal lesions are found commonly in such patients, their detection by diagnostic hysteroscopy should improve compliance with HRT as it would allow individualization of treatment.

Biopsy↗

Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors.

OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment. RESULT(S): In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.

Administration, Cutaneous↗

Estrogen receptor alpha and beta expression in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women.

OBJECTIVE: To assess the expression of messenger RNA (mRNA) for estrogen receptors alpha and beta in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women. DESIGN: In vitro experiment. SETTING: Academic research environment. PATIENT(S): Sixteen consecutively seen women who underwent hysterectomy. INTERVENTION(S): Samples of anterior vaginal walls and uterosacral ligaments were obtained during hysterectomy. MAIN OUTCOME MEASURE(S): Reverse transcriptase-polymerase chain reaction analysis for estrogen receptor mRNA. RESULT(S): Messenger RNA transcripts for estrogen receptor alpha were present in all samples of vaginal walls (16/16) and uterosacral ligaments (16/16). Estrogen receptor beta mRNA was detected in all samples of vaginal walls from premenopausal women (12/12) but in none of those from postmenopausal women (0/4). Estrogen receptor beta mRNA was found in most samples of uterosacral ligaments from premenopausal women (10/12) and in some of those from postmenopausal women (2/4). CONCLUSION(S): Estrogen receptors alpha and beta were expressed in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women. Estrogen receptor beta was absent from the vaginal walls of postmenopausal women.

Adult↗

Effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction.

OBJECTIVE: To evaluate the acute effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction. DESIGN: Prospective, double-blind, placebo-controlled, clinical study. SETTING: Cardiology and postmenopausal outpatient clinics of a university hospital. PATIENT(S): Thirty postmenopausal women with hypertension (diastolic blood pressure of >90 mm Hg) and left ventricular diastolic dysfunction (mitral E/A ratio [the ratio of peak velocity of early mitral diastolic filling to late diastolic filling] of <1 and isovolumic relaxation time of >100 ms) were included in the study. Thirty normotensive postmenopausal women with normal left ventricular diastolic function served as the control group. INTERVENTION(S): Conjugated equine estrogen (0.625 mg) was given orally. Left ventricular diastolic function was assessed by Doppler echocardiography at baseline and 3 hours after the administration of estrogen. MAIN OUTCOME MEASURE(S): Left ventricular diastolic filling as assessed by Doppler echocardiography. RESULT(S): Estrogen had no effect on heart rate or blood pressure in either study group. The baseline E/A ratios were 0.72 +/- 0.26 and 1.22 +/- 0.30, and the isovolumic relaxation times were 122 +/- 18 ms and 89 +/-14 ms in the hypertensive and normotensive groups, respectively. Estrogen had no significant effect on any of the Doppler parameters in the normotensive group. In the hypertensive group, there was a trend toward normalization of the E/A ratio (from 0.73 +/- 0.11 to 0.84 +/- 20) and a significant improvement in the isovolumic relaxation time (from 124 +/- 20 ms to 105 +/- 13 ms) in response to the administration of estrogen compared with placebo. CONCLUSION(S): A single dose of oral estrogen caused a significant improvement in left ventricular diastolic filling in hypertensive postmenopausal women with diastolic dysfunction.

Blood Pressure↗

Hormone replacement therapy increases renal kallikrein excretion in healthy postmenopausal women.

Hypertension and its related increase in cardiovascular morbidity in postmenopausal women is a major public health problem. The hypotensive property of urinary kallikrein has been described since 1909. Despite the controversy surrounding the effects of hormone replacement therapy on blood pressure regulation, its mechanisms remain incompletely understood, and no evidence has yet been provided for its effects on renal kallikrein excretion in postmenopausal women. In a double-blind, randomized study we examined the effects of hormone replacement therapy in the form of 2 mg 17-beta estradiol (ERT) or 2 mg 17-beta estradiol combined with continuous 5 mg medroxyprogesterone acetate (HRT) on urinary kallikrein excretion in postmenopausal women. Thirty-nine postmenopausal women collected their urine for 24 hours on two separate occasions 3 months apart. During the 3 month period women were randomized to placebo, ERT, or HRT. Urine samples were assayed for kallikrein activity, normalized to urine creatinine and expressed as mU/gm creatinine. Urinary kallikrein excretion increased significantly after 3 months in the ERT (p < 0.001) and HRT (p < 0.01) groups, and decreased non-significantly in the placebo group (p > 0.06). There were no significant blood pressure changes after 3 months of therapy. The findings demonstrate that hormone replacement therapy in the form of estrogen or estrogen combined with continuous medroxyprogesterone is effective in increasing urinary kallikrein excretion. Given that a decrease in kallikrein excretion may mark risk for development of hypertension, the findings of this study are of value in demonstrating a novel mechanism underlying cardioprotective properties of postmenopausal hormone replacement therapy in women without pre-existing coronary disease.

Aged↗

Postmenopausal hyperthecosis: functional dysregulation of androgenesis in climacteric ovary.

BACKGROUND: Hyperandrogenism of ovarian origin is rare in postmenopausal women. However, there is evidence that the ovaries of postmenopausal women are active endocrine glands, secreting mainly androgens. CASE: A postmenopausal woman sought treatment for progressive hirsutism. Endocrine evaluation revealed androgen excess. Transvaginal ultrasound revealed enlarged ovaries. Hysterectomy and bilateral oophorectomy were recommended. However, surgery had to be withheld for 6 months while the patient recovered from an acute myocardial infarction. In the interim, the patient's hyperandrogenemia was successfully treated with monthly injections of the gonadotropin-releasing hormone agonist (GnRH), leuprolide acetate. CONCLUSION: This report illustrates the potential for postmenopausal ovaries to become active androgen-secreting endocrine organs. It also demonstrates the efficacy of pharmacologic intervention for postmenopausal ovarian hyperthecosis when the patient is a poor surgical candidate.

Algorithms↗

Human papillomavirus infection in postmenopausal women with and without hormone therapy.

OBJECTIVE: To determine whether postmenopausal hormone therapy is associated with high-risk human papillomavirus (HPV) infection. METHODS: The detection rate of HPV DNA was studied in cellular residue from liquid-based collection tubes taken from 180 postmenopausal hormone users attending a menopausal clinic and 126 postmenopausal nonusers. The samples were analyzed with a hybrid capture technique using a mix of high- to intermediate-risk viral RNA probes. In all patients, information on potential confounding factors for HPV infection, including sociodemographic, reproductive, and gynecologic characteristics, was obtained. RESULTS: The prevalence of HPV DNA in this cohort of postmenopausal women was 1% (three of 306); only two of the 180 current users and one of the 124 nonusers tested positive. Only one of the three women with HPV-positive tests had lesional tissue (i.e., vulvar condylomata acuminata). The remaining two HPV-positive women had negative cytology, colposcopy, and biopsy. In all three cases, viral burden was low, about 10 pg per cellular sample. The very low HPV prevalence precluded the analysis of correlation with age, ethnicity, education, sexual history, smoking, history of abnormal Papanicolaou smear, therapy for HPV-related lesions, and contraceptive use. CONCLUSION: Identification of high-risk HPV types in post-menopausal women is rare, as detected by hybrid capture in cellular residue from the liquid-based cytology-collection system. Postmenopausal hormone therapy does not appear to promote viral replication or the risk of carrying high-risk HPV DNA or related lesional tissue in the lower genital tract.

Aged↗

Expression of estrogen receptor alpha and beta in myometrium of premenopausal and postmenopausal women.

Although a clear role for estrogen receptor (ER) alpha has been established, the contribution of ERbeta in estrogen-dependent development, growth and functions of the myometrium is not understood. As a first step towards understanding the role of ERbeta, we have examined the expression of ERalpha and ERbeta in the human myometrium. With competitive RT-PCR assays, the level of ERbeta mRNA was 10-200 times lower than that of ERalpha mRNA in both premenopausal and postmenopausal myometrium. In premenopausal myometrium, the expression pattern of ERbeta mRNA during the menstrual cycle was similar to that of ERalpha mRNA, with highest levels in peri-ovulatory phase. In postmenopausal myometrium, ERbeta mRNA was significantly higher than it was in premenopausal myometrium, while the level of ERalpha mRNA was lower. The net result was a change in the ratio of ERbeta to ERalpha mRNA expression. The ratio changed from 0.6-1.5 in premenopausal to 2.5-7.6 in postmenopausal myometrium. In premenopausal women, the gonadotropin releasing hormone analogue, leuprorelin acetate, elicited a decrease in ERalpha and an increase in ERbeta mRNA expression to cause a postmenopausal receptor phenotype. Estradiol, on the other hand, reversed ERalpha and ERbeta mRNA expression and their ratio in postmenopausal myometrium to those of premenopausal myometrium. Immunohistochemical staining and Western blot analysis of ERalpha and ERbeta with semiquantitative analysis showed good agreement between mRNA and protein levels. The data indicate that coordinated expression of ERalpha and ERbeta might be necessary for normal estrogen action in myometrium. Furthermore, estrogen appears a dominant regulator of both receptors in the myometrium.

Adult↗

MPA and postmenopausal coronary artery atherosclerosis revisited.

Whether progestins, particularly medroxyprogesterone acetate (MPA), attenuate the cardiovascular benefits of postmenopausal estrogen replacement therapy (ERT) has been controversial for over a decade. Concerns related first to findings that MPA attenuated increases of high density lipoprotein cholesterol (HDLC) concentrations of postmenopausal women compared to conjugated equine estrogen (CEE) alone. That observation was followed by early cynomolgus monkey studies that suggested MPA decreased estrogen's cardiovascular benefits (vascular reactivity and coronary artery atherosclerosis inhibition). In a more recent and larger trial with cynomolgus monkeys, no differences were seen in the coronary artery atherosclerosis protective effect of CEE when MPA was co-administered (HRT). The lack of attenuation of ERTs benefits by progestins has also been seen in at least three studies of carotid artery intima-media thickness (IMT) of postmenopausal women. Additionally, the majority of studies of vascular reactivity of postmenopausal women have not found differences when CEE is given alone or with MPA. Seven observational studies of cardiovascular outcomes of postmenopausal women permit separate consideration of ERT versus HRT use; there is no evidence of attenuation of ERTs benefits by progestin use. In conclusion, it is evident that the current experimental, clinical, and observational data do not provide evidence that progestins attenuate estrogen's cardiovascular benefits.

Animals↗

Fracture incidence in postmenopausal women with primary hyperparathyroidism.

BACKGROUND: The association of bone loss and increased fractures in postmenopausal women with minimally symptomatic hyperparathyroidism has not been clearly defined. This study was done to determine the frequency of fractures in postmenopausal women with hyperparathyroidism. METHODS: Forty-six postmenopausal women who had undergone parathyroidectomy for hyperparathyroidism during a 5-year period (1986 to 1991) were interviewed, and their medical records were examined to determine their fracture history. Forty-four postmenopausal women without hyperparathyroidism were contacted by random digit dialing and interviewed as controls. RESULTS: The groups were comparable with regard to age, weight, height, race, and age at menopause. Medical conditions and medication use were also similar, except for more reports of hypothyroidism in the hyperparathyroidism group (p = 0.05). Only 13% of women presented for treatment because of bone concerns, either fractures (9%) or low bone density (4%). However, on interview, 48% of the patients with hyperparathyroidism reported fractures compared with 25% of the controls (p = 0.02), a difference that remained even when those presenting with bone disease were excluded (p = 0.05). Of those with fractures, multiple fractures occurred in 36% of patients with hyperparathyroidism compared with 9% of controls and generally occurred after minor rather than major trauma (92% versus 45%, p = 0.002). Appendicular skeletal sites were reported for 86% of hyperparathyroidism group's and 92% of control group's fractures. Moreover, 50% of patients with hyperparathyroidism reported height loss compared with 27% of the control group (p = 0.05). CONCLUSIONS: This study shows that postmenopausal women with hyperparathyroidism reported more fractures and height loss than the control group, even when patients with hyperparathyroidism who presented because of bone disease were excluded.

Aged↗

Proopiomelanocortin gene expression is decreased in the infundibular nucleus of postmenopausal women.

Previous studies have shown that estrogen withdrawal decreases the secretion of beta-endorphin from the monkey hypothalamus. In addition, there are consistent age-associated changes in beta-endorphin neurons in the rodent. Based on these findings, we hypothesized that the activity of hypothalamic beta-endorphin neurons would be decreased in the hypothalamus of postmenopausal women. In the present study, we examined the expression of proopiomelanocortin (POMC) mRNA, the precursor mRNA for beta-endorphin, in the medial basal hypothalamus of premenopausal and postmenopausal women. Every 20th sagittal section through the hypothalamus was hybridized with a synthetic [35S]labeled, 48-base oligonucleotide probe complementary to POMC mRNA. Labeled neurons were counted and their somatic profile areas were measured with an image-combining computer microscope system. The number of POMC mRNA-containing neurons/section in the infundibular nucleus was reduced by 65% in postmenopausal women. In contrast, there was no significant difference in the number of neurons expressing POMC gene transcripts in the retrochiasmatic region. The POMC neurons in the retrochiasmatic area were also distinct morphologically from those in the infundibular nucleus. The differences between the infundibular and retrochiasmatic regions suggest that functional subgroups of POMC neurons exist in the human hypothalamus. Our findings provide evidence that the activity of hypothalamic POMC neurons is decreased in the infundibular nucleus of postmenopausal women. Both aging and gonadal steroid withdrawal may contribute to the decline in POMC gene expression in postmenopausal women.

Adult↗

1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with postmenopausal osteoporosis.

A decrease in intestinal calcium absorption, in spite of normal serum calcitriol levels, has been reported in postmenopausal osteoporotic women, raising the possibility of an intestinal resistance to the hormone. The mechanism responsible for it could lie at the receptor or postreceptor level. Intestinal receptors are difficult to study on clinical settings, but calcitriol receptors have been found in peripheral blood mononuclear cells (PBMC). We have studied the PBMC calcitriol receptors by means of Scatchard analysis in 11 postmenopausal osteoporotic women without any treatment and in 12 normal postmenopausal women of similar age. No differences were found in the dissociation constant (Kd) or the concentration of binding sites (Nmax) (Kd in patients: 0.90 +/- 0.75 x 10(-10) M; Kd in controls: 0.85 +/- 0.40 x 10(-10) M; Nmax in patients: 2.4 +/- 1.2 fmol/10(7) cells; Nmax in controls: 2.1 +/- 0.6 fmol/10(7) cells), supporting the contention that the disorder responsible for the resistance to calcitriol in postmenopausal osteoporotic women is located at the postreceptor level. In addition, our study included five postmenopausal osteoporotic women treated with calcitriol (0.5 microgram/day). The number of calcitriol receptors was increased in this group (Nmax: 3.9 +/- 2.0 fmol/10(7) cells vs. 2.1 +/- 0.6 fmol/10(7) cells; P = 0.02).

Adult↗

Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography.

OBJECTIVE: The aim of the present study was the evaluation of simple reproducible sonomorphological criteria for the preoperative evaluation of ovarian tumors in postmenopausal women by use of transvaginal sonography. STUDY DESIGN: Postmenopausal women (> or =1 year of secondary amenorrhea) with ovarian tumors (n=378; tumors > or =3 cm and <3 cm but with solid parts) were examined in a prospective study by transvaginal sonography prior to surgery between 1987 and 1993. The sonomorphological criteria were correlated with the histological findings of the tumors. RESULTS: Of all ovarian tumors in postmenopausal women, 6.3% were functional cysts (follicular or corpus luteum cysts). Almost all of them were detected within the first 5 years of postmenopause. The other ovarian tumors were diagnosed as retention cysts (17.5%), benign neoplasms (39.4%), and malignant tumors (36.8%). Simple ovarian cysts (monolocular, smooth inner wall) represented sonomorphologically the second most frequent type of ovarian tumors in postmenopausal women (35.7%). Of these tumors, 9.6% were diagnosed as malignant. CONCLUSIONS: Simple reproducible sonomorphological criteria proved to be a useful clinical parameter in the preoperative evaluation of ovarian tumors.

Adult↗

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women.

OBJECTIVE: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. METHODS: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17beta-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. RESULTS: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: -11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1 (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. CONCLUSION: Treatment of perimenopausal and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.

Adult↗

Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen.

BACKGROUND: Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women. METHODS: Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1 years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiselius's index (AP(CaOx)) and calcium/citrate ratio. RESULTS: After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2 +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/- 3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively. CONCLUSIONS: Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Aged↗