Estrogen replacement decreases the set point of parathyroid hormone stimulation by calcium in normal postmenopausal women.

Estrogens decrease serum total and ionized calcium (Ca) concentrations in postmenopausal women with or without primary hyperparathyroidism, but cause little or no increase in serum PTH suggesting a modification of the relationship between the two. In order to define this relationship, we studied the effect of conjugated estrogens on total and ionized serum Ca and serum PTH concentrations in five normal postmenopausal women, before and after 3, 11, and 23 weeks of therapy. Dynamic tests of parathyroid gland function, based on 2-h iv infusions of CaCl2 and NaEDTA, were performed at each time. Total and ionized serum Ca and carboxylterminal PTH were measured every 15 min during the infusions, and parathyroid function was evaluated by a nonlinear 4-parameter mathematical model. Estrogen therapy caused decreases in serum total [2.36 +/- 0.04 (SD) mmol/L, baseline vs. 2.19 +/- 0.05 mmol/L, 23 weeks, P less than 0.005) and ionized calcium (1.27 +/- 0.01 mmol/L, baseline vs. 1.21 +/- 0.02 mmol/L, 23 weeks, P less than 0.005]; the decreases were evident at 3 weeks and persisted for the duration of the study. Serum PTH concentrations did not change (8.94 +/- 1.84 pmol/L, baseline vs. 8.98 +/- 2.38 pmol/L, 23 weeks). Three parameters of the parathyroid function, the maximal response to hypocalcemic stimulation, the nonsuppressible fraction of circulating PTH, and the slope of PTH on calcium at the set point were not affected by estrogen treatment. The fourth parameter, the set point of PTH stimulation by serum total calcium (2.16 +/- 0.04 mmol/L, baseline vs. 1.97 +/- 0.07 mmol/L, 23 weeks, P less than 0.0166) or by serum ionized Ca (1.19 +/- 0.04 mmol/L, baseline vs. 1.12 +/- 0.03 mmol/L, 23 weeks, P less than 0.01), was decreased by estrogen treatment. This was evident at the earliest time point studied and persisted thereafter. The decrease in ionized Ca set point only explained 40% of the decrease in total calcium set point, the remaining 60% being related to hemodilution of plasma protein during therapy. We conclude that estrogen replacement can influence parathyroid function in postmenopausal women by resetting the set point of PTH stimulation by ionized Ca. This in turn could contribute to the estrogen-induced changes in their Ca balance.

Single oral dose of ornidazole in women with vaginal trichomoniasis.

Fifty-nine women with trichomonal vaginitis were randomly allocated to receive treatment with a single oral dose of either 0.5, 1.0, or 1.5 g of ornidazole. One week after treatment, a parasitologic cure was observed in 100% of patients treated with 1.5 g, in 95% of patients treated with 1.0 g, and in 65% of patients given 0.5 g. At the one-month follow-up visit, the cure rate remained at 100% for the 1.5-g dose group but dropped to 85 and 45% in the 1.0- and 0.5-g dose groups, respectively. The disappearance of symptomatic complaints was also dose related: the clinical cure was 100, 85, and 40% at the first follow-up visit and 89, 80, and 30% at the second follow-up visit. Adverse effects of mild or moderate severity were reported by 13 patients. These were encountered mostly in the 1.5- and the 1.0-g dose groups. The most frequent adverse effects were dizziness and gastrointestinal distress. Laboratory safety test did not reveal any significant toxicity. This study confirms that single-dose treatment of trichomoniasis with an oral dose of 1.5 or 1.0 g of ornidazole is effective and well tolerated.

Comparison of transdermal and oral sequential gestagen in combination with transdermal estradiol: effects on bleeding patterns and endometrial histology.

OBJECTIVE: To assess prospectively the effect on bleeding patterns, transformation of the endometrium, and rate of endometrial hyperplasia of transdermal norethisterone acetate when administered sequentially in combination with transdermal estradiol (E2), and to compare it to a regimen using oral medroxyprogesterone acetate. METHODS: Two hundred eighteen women were randomized to receive either transdermal E2 0.05 mg/day for 14 days followed by transdermal E2 0.05 mg/day plus transdermal norethisterone acetate 0.25 mg/day for 14 days, or transdermal E2 0.05 mg/day for 25 days with the addition of oral medroxyprogesterone acetate 10 mg/day on days 16-25, followed by a 3-day treatment-free period. Treatment was planned for 13 cycles of 28 days. The subjects kept daily bleeding diaries, and endometrial biopsies were taken before and at the end of treatment. RESULTS: The mean duration of bleeding (regular) induced by the gestagen was 7.33 days in the transdermal gestagen-treated group, which was 1.54 days longer than in the oral gestagen-treated group (P = .0001). The mean cycle day of onset was 25.74. Bleeding was spotting or light in the transdermal group in 77% of the days in which bleeding occurred. When comparing the two groups, there were no differences in the overall mean cycle day of onset or in the intensity of gestagen-induced bleeding. Breakthrough (irregular) bleeding episodes occurred in 42% of the transdermal subjects, lasted a mean of 4.18 days, and were spotting or light in 87% of the days when they occurred. There were no differences between the treatment groups. There was only one case (1.3%) of confirmed simple hyperplasia and five cases of failure of gestagenic transformation of the endometrium in 77 women treated for a mean of 367 days with transdermal gestagen. CONCLUSION: A transdermal system delivering a combination of E2 and norethisterone acetate for 14 days in sequence with E2 delivered transdermally for 14 days produced bleeding patterns that are clinically acceptable and comparable to those produced by oral medroxyprogesterone acetate given in sequence with E2 delivered transdermally for 25 days. The use of the combination system was not associated with a significant risk of endometrial hyperplasia.

Cardiovascular risk factors during sequentially combined 17 beta oestradiol and dydrogesterone (Femoston); results from a one-year study in postmenopausal women.

OBJECTIVES: To assess the effects of Femoston (2 mg micronised 17 beta oestradiol daily, sequentially combined in one tablet with 10 mg dydrogesterone for 14 days per 28 day cycle) on the serum lipid profile of postmenopausal women. METHODS: 188 healthy postmenopausal women with intact uteri (aged 40 to 65 years) were enrolled in an open, multicentre, one-year study. Serum lipids and lipoproteins were measured at baseline and after 3, 6 and 12 months. RESULTS: A total of 155 women completed the one-year study. Mean serum levels of total cholesterol and low-density lipoprotein (LDL)-cholesterol were significantly reduced (P < 0.01) at all assessments compared with baseline; the reductions observed at the final assessment were 5 and 20%, respectively. A significant increase of 20% (P < 0.01) was seen in high-density lipoprotein (HDL)-cholesterol levels by month 12. Mean levels of triglycerides were also increased (p < 0.01). Blood pressure and heart rate remained unchanged throughout the study. CONCLUSIONS: The results show that the overall effects of Femoston on the serum lipid profile are comparable to those found with oestrogen therapy alone and should reduce the risk of cardiovascular disease in postmenopausal women.

Metabolic effect of two hormonal preparations in postmenopausal women.

OBJECTIVES: To compare the metabolic and endocrinological effects of estradiol valerate/cyproterone acetate (EV/CPA) to a regimen of conjugated estrogens/medroxyprogesterone acetate (CE/MPA) in postmenopausal women. METHODS: Lipid profile, endocrinological parameters, coagulation factors, renin and angiotensinogen were followed in postmenopausal women randomized to EV/CPA or CE/MPA during 12 cycles. RESULTS: Following 12 cycles of treatment, total plasma cholesterol decreased more with EV/CPA than with CE/MPA. Low-density cholesterol decreased with EV/CPA while it increased with CE/MPA. High-density cholesterol remained fairly unchanged, and triglycerides increased significantly in both groups. Estradiol and estrone levels increased significantly more with EV/CPA than with CE/MPA while the sex-hormone-binding globulin increased more with CE/MPA. Follicle stimulating and luteinizing hormone levels also decreased significantly. Total testosterone and dihydroepiandrosterone sulfate remained stable. Total levothyroxine serum levels increased significantly, but thyroid stimulating hormone and triiodothyronine levels remained stable. Coagulation parameters also remained stable. Angiotensinogen increased, while plasma renin activity and blood pressure remained unchanged. CONCLUSION: It is concluded that both EV/CPA and CE/MPA produce favourable metabolic effects. A better lipid profile, compatible with decreased cardiovascular risk, is observed with the EV/CPA regimen. Higher circulating estrogen levels may explain in part this observation.

Five years experience of intrauterine contraception with the Nova-T.

This study was conducted to evaluate the clinical performance of the Nova-T IUD. The insertion period was from November 1981 to November 1982. Two-hundred-and-one (201) consecutive IUDs were inserted in women attending a family planning clinic and they were followed for a period of 5 years. Most events occurred in the first 2 years of the study and there were no pregnancies in the 3rd, 4th or 5th year. The pregnancy rate after 5 years was 3.2 or a Pearl index of 1.21 which is very good compared to other methods of contraception now available. Our conclusion is that the Nova-T IUD is an excellent method of contraception and it can be left in place for a period of 5 years.

PIP: This study was conducted to evaluate the clinical performance of the Nova-IUD. The insertion period was from November 1981 to November 1982. 201 consecutive IUD's were inserted in women attending a family planning clinic at a university hospital in Canada and they were followed for a period of 5 years. Most events occurred in the first 2 years of the study and there were no pregnancies in the 3rd, 4th or 5th year. The pregnancy rate after 5 years was 3.2 or a Pearl index of 1.21 which is very good compared to other methods of contraception now available. Our conclusion is that the Nova-T IUD is an excellent method of contraception and it can be left in place for a period of 5 years.

Cyproterone acetate/ethinyl estradiol in the treatment of acne. A comparative dose-response study of the estrogen component.

The investigators compared 2 mg cyproterone acetate (CPA) in combination with either 0.035 mg or 0.050 mg ethinyl estradiol (EE2) (Diane -35 versus Diane -50) in the treatment of acne. Both formulations of Diane were highly effective in improving acne, even in women who had been refractory to other types of medication. Cycle control with both formulations was excellent and adverse effects were generally mild and confined to the first two cycles of treatment. Mean plasma lipid levels increased with both treatments, yet most individual values remained within normal limits after one year of therapy while the LDL-cholesterol/HDL-cholesterol ratio was stable throughout the study period. Plasma testosterone and DHEA-S levels paralleled the decline in the clinical severity of the acne. There was no loss of clinical effectiveness with Diane -35 and it provided the advantage of a 30% decrease in the amount of estrogen.

[Is a hysterectomy justifiable to prevent post-tubal ligation syndrome?]. / Une hystérectomie est-elle justifiable pour prévenir le syndrome post-ligature?

PIP: Among 2057 tubal ligations performed between 1971-75 in "Hopital Saint-Luc" in Montreal, 78 patients had to be readmitted for hysterectomy. The main indication for hysterectomy among these patients was for menstrual disorders (65%). These menstrual disorders were present at the moment of the tubal ligation in about half of the patients. Among the patients who had to be reoperated for hysterectomy for menstrual disorders and who were asymptomatic at the momemt of their tubal ligation, 88% were using oral contraceptives for a mean period of 5.8 years. The low incidence of hysterectomy post-tubal ligation (3.8%) does not seem to justify a total hysterectomy to prevent what has been described as the "post tubal ligation syndrome" in the patients who are asymptomatic and desire a permanent sterilization. (Author's modified)^ieng

[Non-instrumental traumatic rupture of the hypopharynx and the cervical esophagus]. / Les ruptures traumatiques non instrumentales de l'hypopharynx et de l'oesophage cervical

We present four cases of non-instrumental traumatic ruptures of the hypopharynx and the esophagus. Three are ruptures with closed neck and one with a rupture associated with a cervical wound. A conjoined lesion of the airway is usual, except in one of our observation. All people injured come from car, sport, or work accidents. The esophageal wound, contaminating the mediastinum, is life-threatening and requires a rapid therapeutic solution: wide drainage tube and antibiotics. The diagnosis, often difficult due to poor symptomatology, must be thought of when there is any severe trauma of the cervical region.

Screening for thyroid disease at the menopausal clinic.

The prevalence of hypothyroidism has been reported to increase with age and to attain up to 10% in older women. We wanted to verify whether routine screening for thyroid disease could be justified in a specific sub-population of aging women, those consulting for the first time at a menopausal clinic. Standard thyroid profiles (Total T4, T3 uptake, calculated free thyroxine index (FTI), and sensitive thyroid stimulating hormone (TSH)) were obtained in 500 consecutive patients seen at such a clinic over 18 months. Thyroid microsomal and thyroglobulin antibody titers were also obtained in over half of them. Twenty-three carefully selected, age-matched, peri-menopausal hospital employees served as a reference group for the TRH response test. Thirteen women (2.6%) had previously diagnosed hypothyroidism but 4 of them were found to be sub-optimally treated. Fifty other subjects (10%) had out-of-range screening TSH levels, 7 below and 43 over the assay reference range. In the former, 3 (0.6%) were found to be hyperthyroid while in the latter 8 (1.6%) were found to be overtly hypothyroid based on TSH levels over 10 mU/L and accompanying signs and symptoms. Twelve other subjects (2.4%) were found to have sub-clinical hypothyroidism based on a positive TRH response test and a significantly increased prevalence of goiter and positive antibody titers. The remaining 23 patients had a normal TRH response test, although their mean TSH level at 30-min post-TRH and the prevalence of positive antibody titers were significantly higher than those of the control group and normal subjects respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of cephalosporins as antibiotic prophylaxis in cesarean section]. / Utilisation des céphalosporines comme antibioprophylaxie lors de césariennes.

Cefoxitin, a second-generation cephalosporin, was compared with cefazolin, a first-generation cephalosporin, and a placebo in a prospective, double-blind study of antibiotic prophylaxis in women undergoing nonelective cesarean section. In the groups that received cefazolin or the placebo there eas no statistically significant change in colonization of the cervix by aerobic bacteria by the fourth day after the operation, but there was a statistically significant increase in colonization by anaerobes. Cefoxitin had the opposite effect. Of the 14 postoperative infections in 11 patients, significantly more were in patients who had received the placebo; the numbers were too small to show a difference in effectiveness between the two antibiotics. Of the microorganisms implicated as the infectious agents, group B Streptococcus was the most frequent aerobe, and Peptostreptococcus and Bacteroides bivius were the most frequent anaerobes. Among the 15 patients for whom at least one perioperative specimen yielded positive culture results, a postoperative infection developed in 5 of the 6 who received the placebo, 2 of the 4 who received cefazolin and 1 of the 5 who received cefoxitin.

Raloxifene HCl is not stimulatory in the endometrium as assessed by the blaustein criteria and an estrogenicity scoring system.

Introduction: Raloxifene, a selective estrogen receptor modulator (SERM), acts as an estrogen agonist in the bone and on serum lipids and an estrogen antagonist in breast tissue. The effect of raloxifene on the endometrium of postmenopausal women is a key factor in determining its clinical application.Objectives: The objectives are to determine and compare the histologic outcomes of endometrial samples from healthy postmenopausal women receiving either a high dose of raloxifene or hormone replacement therapy (HRT).Design: The current study is a 24-month, multicenter, double-blind, randomized study of 136 healthy postmenopausal women randomized to receive either raloxifene 150 mg/day (RLX) or continuous combined HRT (Premarin(R) 0.625 mg/day and Provera(R) 2.5 mg/day).Materials and Methods: Endometrial samples obtained by Pipelle biopsy at baseline and endpoint were evaluated using Blaustein's criteria (Kurman RJ, editor Blaustein's pathology of the female genital tract. 1994), which is composed of descriptive diagnostic categories and a newly developed estrogenicity scoring system to quantify subtle morphologic changes in the postmenopausal endometrium (Boss et al. Am J Obstet Gynecol, in press). All subjects with adequate baseline and post-baseline endometrial samples were included in the analyses. The results from the 12-month interim analyses are reported and the Blaustein's criteria and the estrogenicity scoring system are compared.Results: Overall, 95.2% of the baseline biopsies were normal. At endpoint 30.6% of the subjects in the HRT group with normal baseline biopsies developed proliferative endometrium and 2.8% developed a polyp, while none in the RLX group developed either. Histological evaluation of stromal and glandular features revealed substantially lower estrogenicity scores in the RLX group. As shown in the table, a high degree of agreement was observed between the estrogen effect grades and the Blaustein's descriptive diagnostic categories at endpoint as shown by a Spearman correlation coefficient of 0.75 and a Kappa coefficient of 0.91.Conclusion: Results from the 12-month interim analyses reveal that, in contrast to HRT, raloxifene does not have stimulatory effects on the endometrium. Also, there is high degree of agreement between Blaustein's criteria and the estrogenicity scoring system used to evaluate endometrial histology.

Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women.

OBJECTIVE: We sought to compare the uterine effects of raloxifene with those of continuous-combined hormone replacement therapy. STUDY DESIGN: This randomized, double-blind 24-month study involved 136 postmenopausal women who received raloxifene 150 mg/d or conjugated equine estrogens 0.625 mg/d with medroxyprogesterone acetate 2.5 mg/d. After baseline evaluations, endometrial biopsy specimens were obtained, and endometrial thickness was measured annually by means of transvaginal ultrasonography. Statistical analyses were performed with an intention-to-treat approach. RESULTS: In the raloxifene group at the end point of the study 94.4% of biopsy specimens showed normal benign postmenopausal endometrium and 5.6% were classified as benign stimulatory endometrium. In the continuous-combined hormone replacement therapy group at the end point of the study 78.7% of biopsy specimens showed normal benign postmenopausal endometrium, 19. 1% were classified as benign stimulatory endometrium, and 2.1% showed benign abnormal postmenopausal endometrium. Mean endometrial thickness was unchanged from baseline with raloxifene and was increased significantly by 0.5 mm at 12 months with continuous-combined hormone replacement therapy. CONCLUSION: Raloxifene 150 mg/d did not increase endometrial thickness or cause endometrial proliferation in healthy postmenopausal women.

Premenopausal bone mineral content relates to height, weight and calcium intake during early adulthood.

The influence of dietary and anthropometric factors on bone mineral content was studied in 183 healthy premenopausal French-Canadian women aged between 40 and 50 years and living in the same area. Dietary evaluation of their calcium (Ca), caffeine and alcohol intake since the age of 20 was performed in all cases. Age, height, weight, exercise level, cigarette smoking, parity and estrogen were also recorded. Bone mineral content of the L2 to L4 vertebrae (BMCL, n = 183) and forearm (BMCF, n = 137) were measured respectively by dual and single photon absorptiometry. While stepwise regression analysis showed a significant relationship between total BMCL and height, weight and Ca intake, this only occurred with weight and Ca intake when BMCL was corrected for height of L2-L4 (BMCL/cm) or for bone scan area of L2-L4 (BMCL/cm2). BMCF expressed per unit of length correlated to height only. When subjects were divided into three groups according to their Ca intake (less than 500 mg/day, between 500 and 1000 mg/day and greater than 1000 mg/day), the mean BMC adjusted for significant covariables (height and weight) was statistically different for the low and high intake groups at both sites (BMCF, F = 3.9, P = 0.02; BMCL, F = 4.2, P less than 0.02; BMCL/cm, F = 6.1, P less than 0.005; BMCL/cm2, F = 4.4, P less than 0.02). These findings indicate that, of the variables considered, Ca intake, height and weight were the only significant factors related to bone mass in our homogeneous population. It is therefore suggested that Ca intake in early adulthood influences the axial and appendicular bone mass in premenopausal women.

Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.

A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).

Comparative cervical microflora shifts after cefoxitin or cefazolin prophylaxis against infection following cesarean section.

The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin, cefazolin, or placebo for infectious complications of nonelective cesarean section. Floral shifts occurred post partum, with return of Escherichia coli and Bacteroides fragilis and a decrease in Candida colonization. No significant differences in flora existed preoperatively among patients receiving cefoxitin, cefazolin, or placebo, but by day 4, both antibiotic groups had greater enterococcal colonization. This difference was more marked with cefoxitin than with cefazolin. No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups. Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization. Results of this study indicate that a three-dose cephalosporin prophylactic regimen resulted in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group. There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anerobic microflora between the cefoxitin and cefazolin groups.