Leisure physical activity is associated with quantitative ultrasound measurements independently of bone mineral density in postmenopausal women.

The purpose of this study was to assess the magnitude of the relationship between leisure physical activity and bone status as measured either by an Achilles ultrasound bone densitometer (QUS) or dual-energy X-ray absorptiometry (DXA) in postmenopausal women. We studied 1162 French Canadian postmenopausal women, aged 33-84 years (mean age 58 years), for QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI)] measured at the right calcaneus, and bone mineral density (BMD) measured at the lumbar spine and femoral neck. Multivariate regression analyses revealed that leisure physical activity level was an independent predictor of the heel QUS parameters and of femoral neck BMD. No such association was observed for BMD of the lumbar spine. Heel QUS parameters (BUA, SOS, SI) and femoral neck BMD adjusted for interfering covariables showed a statistically significant difference between sedentary (less than three sessions/month) and active women (three or more sessions/week) (P < or = 0.001). Furthermore, after adjusting each heel QUS parameters for the mean lumbar spine BMD value, the association observed between leisure physical activity and QUS remained significant. These results suggest that regular leisure physical activity could influence QUS parameters, independently of BMD, and that quantitative ultrasound could be a suitable outcome measure in exercise studies in postmenopausal women.

Bone mineral density in French Canadian women.

This cross-sectional study investigated bone mineral density (BMD) at the lumbar spine (L2-4) and femoral neck in French Canadian women residing in the Quebec city area. Data collection was initiated in 1988 and completed in 1994. A total of 747 French Canadian Caucasian women (16-79 years of age) with no metabolic bone disease were evaluated. BMD measurements were obtained using dual-photon absorptiometry (DPA) or dual-energy X-ray absorptiometry (DXA). Anthropometric measures such as weight, height and body mass index (BMI) were recorded. Medical files provided information on demographic characteristics, hormonal profile and lifestyle habits. Results show a curvilinear trend of BMD with aging. Furthermore, the peak BMD at the lumbar spine (L2-4) was reached at 29 years followed by a stable phase until 35 years, after which BMD started to decrease. The pattern of bone evolution at the femoral neck was different, peak BMD being achieved earlier, at 21 years, while after age 26 years a significant decrease was already observed. Women older than 60 years showed the lowest BMD. Regression analysis showed that age, weight and height are determinants of BMD at the lumbar spine and explained 33.9% of inter-individual variation. At the femoral neck, 29.1% of variation was explained by age and height only. In conclusion, our data suggest that French Canadian women have a different pattern of bone loss at the femoral neck compared with the lumbar spine, according to their mean BMD values.

Elevated concentration and biologic activity of monocyte chemotactic protein-1 in the peritoneal fluid of patients with endometriosis.

OBJECTIVE: To estimate the concentration and the biologic activity of monocyte chemotactic protein-1 (MCP-1) in the peritoneal fluid (PF) of women with and without endometriosis. DESIGN: A case control study was conducted. SETTING: Gynecology clinic and Laboratories of endocrinology of reproduction and immunology. PATIENTS: Women presenting for infertility, pelvic pain, or tubal ligation in which endometriosis was diagnosed at laparoscopy (n = 36) and normal fertile controls presenting for tubal ligation (n = 21). INTERVENTIONS: Collection of PF via laparoscopy. MAIN OUTCOME MEASURES: Determination of PF concentrations of MCP-1 by an ELISA and evaluation of its monocyte chemotactic activity using a human hystiocytic cell line (U937). RESULTS. The concentration of MCP-1 (median, range of values) was increased in the PF of endometriosis patients (283, 0 to 1,930 pg/mL; conversion factor to SI unit, 0.155) compared with the control group (140, 0 to 435 pg/mL). The most significant elevation of MCP-1 levels was found in the stage II of the disease (371, 200 to 1,930 pg/mL). An increased chemotactic activity for monocytes (mean number of migrating cells/mm2 +/- SD) also was found in stages I (1,460 +/- 312) and II (1,541 +/- 336) of the disease when compared with fertile controls (393 +/- 56). Forty percent to 53% of this activity was inhibited in the presence of an antibody specific to MCP-1. CONCLUSIONS: These observations are consistent with previous data indicating increased leukocyte chemotaxis in the PF of patients with endometriosis and suggest that MCP-1 may play a relevant role in the peritoneal inflammatory reaction associated with the disease.

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis. LE Group d'Investigation en Gynecologie.

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and /or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 +/- 0.06 and 0.46 +/- 0.06) compared with that in women without endometriosis (0.62 +/- 0.08 and 0.75 +/- 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 +/- 0.07 and 0.47 +/- 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility.

Decreased amounts of antibodies to 22 and 18 kDa antigens in the peritoneal fluid of patients with endometriosis

Accumulated evidence implicates immunological alterations in endometriosis. The purpose of this study was to look for variations in antibodies to distinct antigens in peritoneal fluid of women with and without endometriosis. Peritoneal fluid was aspirated from 17 women undergoing laparoscopy for tubal ligation and 37 patients complaining of symptoms of pain and/or infertility. Peritoneal fluid antibodies to a standard preparation of peritoneal fluid antigens were detected by Western blot analysis using peroxidase-labelled anti-human immunoglobulin G antibodies specific to the Fc region. Antibodies to distinct antigens were quantified by estimating the ratio of the relative optical density between samples and a standard amount of antibodies. Marked changes were found in the antibody detection to two antigens having apparent molecular weights of 22 and 18 kDa. The intensity of the antibody signal was significantly weaker in the peritoneal fluid from endometriosis patients (0.36 ± 0.06 and 0.46 ± 0.06) compared with that in women without endometriosis (0.62 ± 0.08 and 0.75 ± 0.06). It was also weaker in patients without endometriosis presenting with infertility (0.36 ± 0.07 and 0.47 ± 0.08), but only the 18 kDa antigen result was significant. After adjusting for infertility, the P values for the 18 and 22 kDa bands were 0.03 and 0.28 (not significant) respectively in the group of endometriosis patients. These changes were not related to the phase of the menstrual cycle. These data suggest an alteration in the immune response to two distinct antigens in the peritoneal fluid from women with endometriosis and infertility. Further evaluation of these two antigens and their antibodies would be of interest to help understand endometriosis and its associated infertility. Keywords: antibodies/antigens/endometriosis/peritoneal fluid/Western blot analysis

Clinical efficacy and safety of low-dose flutamide alone and combined with an oral contraceptive for the treatment of idiopathic hirsutism.

BACKGROUND AND OBJECTIVE: High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long-term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism. PATIENTS: Flutamide was administered orally in a low dose of 125 mg twice daily for 12 months alone in women with no risk of pregnancy or during the use of an oral contraceptive. MEASUREMENTS: Women were seen every 3 months and were evaluated for hirsutism score, hormone and lipid measurements. DESIGN: The study, which was conducted as a prospective open trial, was proposed to patients with idiopathic hirsutism, that is, with serum androgen levels in normal range and LH/FSH ratio less than 2. RESULTS: A statistically significant decrease in hirsutism score as compared to baseline was observed after only 3 months with either treatment, flutamide alone (16.9 +/- 1.6 vs 14.2 +/- 1.7, P < 0.0001) or the combination of flutamide with OC (15.6 +/- 0.8 vs 11.9 +/- 0.8, P < 0.001). Three months after cessation of treatment a statistically significant decrease from baseline was observed in the two groups. Nevertheless, at 6 months post-treatment this decrease was still significant only in the group who took flutamide in combination with an oral contraceptive. Flutamide alone does not appear to modify the levels of lipoproteins. The association of flutamide with a triphasic formulation significantly increased the HDL-C levels. CONCLUSIONS: This study shows beneficial effects of a low dose of flutamide in women with idiopathic hirsutism. The addition of an oral contraceptive is judicious to prevent pregnancy and reduce recurrence of hirsutism after cessation of flutamide. Peripheral androgenic blockage does not modify lipid profiles and it might reduce the negative effect of oral contraceptive on HDL-C levels. The addition of electrolysis delays the recurrence of hirsutism after cessation of flutamide.

Bone mass in endometriosis patients treated with GnRH agonist implant or danazol.

Before treatment, the trabecular bone mineral content of the lumbar spine and femoral neck was not significantly different between endometriosis patients and age-matched controls (N = 26). In 17 subjects treated with a monthly goserelin implant, serum estradiol (E2) levels were suppressed into the menopausal range. Mean decreases from pre-treatment values in the lumbar spine and femoral neck were -5.7 and -3.8% at 3 months and -8.2 and -7.7% at 6 months of treatment, respectively; lumbar spine values were significantly different (P less than .05) from those of the control group, whose values changed little during the same period. Significant increases over baseline values were also observed in urinary calcium-creatinine ratio and serum alkaline phosphatase. In nine danazol-treated subjects, serum E2 levels were generally within the early follicular-phase range. There were no significant changes in bone assessments. Normal menses returned within 2 months after cessation of either medication. Six months after goserelin treatment, the lumbar spine and femoral neck bone mineral content was still reduced but to values not significantly different from the pre-treatment and control values; urinary calcium-creatinine ratio was decreased, whereas serum alkaline phosphatase was still elevated. The rapid and deep suppression of ovarian steroidogenesis by a monthly goserelin implant induced significant bone loss compared with the control and danazol groups. This loss was not reversed completely 6 months after cessation of treatment, but bone densities at that time were not different from those of controls. Studies of larger numbers of patients followed for longer periods will be required to resolve the question of complete reversibility.

Dose-related inhibition of acute luteinizing hormone response during luteinizing hormone-releasing hormone agonist treatment for uterine leiomyoma.

Twenty-six women with uterine leiomyoma were treated for 6 months with subcutaneous injections of the luteinizing hormone-releasing hormone agonist buserelin. Eight women received 200 micrograms daily, eight women received 350 micrograms daily, and 10 women after initial administration of 200 micrograms every 8 hours for 7 days, 500 micrograms of buserelin was administered daily. After 1, 3, and 6 months of treatment, serum luteinizing hormone levels were measured before and 4 and 8 hours after the administration of buserelin. The area under the curve for acute luteinizing-hormone response was then individually calculated. The inhibition of acute luteinizing hormone response during luteinizing hormone-releasing hormone agonist treatment was proportional to the dosage used and remained constant during the treatment period.

Prolactin receptors in human breast tumors.

Prolactin-binding sites were determined in 759 human breast tumor biopsy specimens. Ovine prolactin (oPRL) was used in the binding assay of 569 tumors with 13% of the tumors showing a positive content with more than 1% specific binding. Human prolactin (hPRL) was utilized for 343 tumors with 36% of the tumors binding 1% or greater of the added radioactivity. When human growth hormone (hGH) was used as the labeled ligand in 95 tumors, only 2% of the tumors specifically bound more than 1% of the hGH. A total of 153 tumors were assayed simultaneously with the use of labeled hPRL and oPRL. Whereas 10.4% of the tumors showed the presence of prolactin-binding sites (greater than 1% specific binding) when oPRL was used, an approximately threefold increase (29.4%) in tumors possessing prolactin receptors was revealed when hPRL was used as the labeled ligand. Therefore, hPRL is the preferred ligand for the assessment of prolactin receptor levels in human breast cancer biopsy specimens.

Response to ovariectomy of N-methyl-N-nitrosourea-induced mammary tumors in the rat.

Noninbred Sprague-Dawley rats bearing N-methyl-N-nitrosourea (MNU)-induced mammary tumors were ovariectomized at 2.5, 3.5, and 4.5 months after the first MNU injection to determine the response to castration as a function of the time of tumor appearance. Tumor number and tumor size recorded at weekly intervals revealed that the tumors in the control rats continued to grow during each of the three observation periods, but that tumor growth was significantly less during the third period. Ovariectomy performed at 2.5 months after the first MNU injection produced a stabilization of tumor number; when performed at 3.5 or 4.5 months, it resulted in a slight decline in tumor number. Although tumor size decreased slightly in rats that were ovariectomized at 2.5 months, many of the tumors regrew during the last 2 weeks of observation. This was not true, however, for rats that were ovariectomized at either 3.5 or 4.5 months after the first MNU injection. The level of receptors for 17 beta-estradiol (E2), progesterone, and prolactin were significantly reduced by ovariectomy. E2 receptors, which ranged from 2.04 +/- 18 to 2.24 +/- 0.24 (mean +/- SEM) pmol/g tissue for the first and second groups of control rats, declined to 0.93 +/- 0.14 pmol/g tissue for the ovariectomized rats at the end of the last interval studied (5.5 mo after the first MNU injection). This study suggests that hormone responsiveness (response to ovariectomy) of MNU-induced mammary tumors increases slightly with the age or time of appearance of the tumors.

Effect of an LHRH analog on growth and hormone receptor levels in DMBA-induced mammary tumors in the rat.

Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat are well known to be hormono-dependent. Daily injections of an LHRH agonist, [D-Ala6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A), 1 microgram daily, for 38 days results in a 35% decrease in the number of tumors present at the beginning of the experiment compared to a decline of 45% after ovariectomy and of 8% in the control group. This is accompanied by a marked reduction in ovarian LH and FSH receptors. LHRH-A treatment also resulted in reduction in the number of progesterone and prolactin receptors in the tumors. In addition, an increase in plasma LH and FSH and a decline in plasma prolactin (PRL) concentrations are observed. The mechanisms by which the LHRH agonist induces its antitumoral effect probably relate to an ovarian desensitization to LH and FSH with a concomitant decrease in circulating levels of estrogen and prolactin, two well known stimuli for the growth of DMBA-induced mammary tumors.

Pancreatic beta cell changes induced by cyproheptadine in vitro.

The effect of cyproheptadine on the structure and function of rat pancreatic beta cells was studied in vitro by culturing isolated islets in media containing the drug (0.5 mM). After 8 days in culture the ultrastructure of islet cells maintained in control media appeared well preserved, being similar to the previously reported for islets kept in long term organ culture. In contrast beta cells from islets incubated in media containing cyproheptadine appeared degranulated and the rough endoplasmic reticulum showed cisternal dilation and vacuole formation. These vacuoles were filled with an electron-dense granular material and their surface was usually studded with ribosomes. These lesions are identical with those produced by the administration of cyproheptadine to rats in vivo. In addition to these findings, increased numbers of lysosomes and myeloid bodies were observed in both alpha and beta cells. Compared with that of the controls, the 24-hour basal insulin secretion of islets cultured in the presence of cyproheptadine was significantly reduced from the 4th day of the study onwards. It is thus concluded that cyproheptadine has direct effects on the morphology and function of the rat pancreatic beta cell.

Effect of glucose and anti-insulin serum on insulin released from adult rat isolated islets of Langerhans in long-term organ culture (fourteen days).

Isolated islets of Langerhans from adult male rats were cultured in media containing either basal (1 gm./ml.) or high glucose (3 mg./ml.), and the media were changed every two days for fourteen days. The insulin released in each medium was measured by a back-titration radioimmunoassay. Insulin secretion was fairly constant in the basal glucose medium and a consistent three-to-sevenfold increase was observed in the alternated or continuous presence of high glucose. Addition of an excess of anti-insulin serum did not change significantly the basal or stimulated release of insulin. The electron microscopic appearance of the islets after fourteen days of incubation showed well-preserved islets both with or without anti-insulin serum. Anti-insulin serum did not alter the ultrastructural aspects of the islets in either basal or high glucose media.