Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort.

OBJECTIVE: To determine the clinical features and microbial aetiology of acute salpingitis in women attending an inner city teaching hospital. DESIGN: Prospective, longitudinal cohort study. SUBJECTS: One hundred and forty-seven women presenting consecutively with acute abdominal pain and clinical signs of acute salpingitis were evaluated microbiologically and laparoscopically. RESULTS: One hundred and four women (70.7%) had acute salpingitis diagnosed at laparoscopy. Other pathological conditions were identified in 20 women (13.6%). No visually identifiable pathology was found in 23 (15.6%). Thirty-five women with acute salpingitis had evidence of pelvic adhesions (33.7%). Bilateral tubal occlusion was present in 6 (5.8%) cases. Chlamydia trachomatis was identified in the genital tract in 40 (38.5%) of the women with acute salpingitis and Neisseria gonorrhoeae in 15 (14.4%). A dual infection was present in eight cases (7.7%). Serological evidence suggested that a further seven women (6.7%) had acute chlamydial infections at the time of diagnosis. C. trachomatis was identified in the genital tract of 5/23 (21.7%) of the women who had no laparoscopic evidence of intra-abdominal pathology. CONCLUSIONS: The responsible care of women with suspected acute salpingitis depends on establishing an accurate diagnosis, so that appropriate therapy can be instigated. This study provides evidence to challenge the outpatient management of acute salpingitis on clinical grounds alone as potentially inadequate. Early laparoscopy in hospitalised women improves diagnostic precision and accurately determines disease severity, providing prognostic information for future fertility. In this urban population, sexually transmitted micro-organisms were the commonest pathogens found in the genital tract of women with acute salpingitis. The high prevalence of C. trachomatis in these women suggests that appropriate chemotherapy for acute salpingitis should always include a specific antichlamydial agent.

A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis.

OBJECTIVE: To compare dydrogesterone with placebos in the treatment of minimal to mild endometriosis. DESIGN: Prospective, double-blind, randomized study. SETTING: Three Obstetrics and Gynaecology Departments in the United Kingdom. PATIENTS: Sixty-two premenopausal women with complaints of pain (n = 12) and infertility with or without pain (n = 50) with minimal to mild endometriosis diagnosed at laparoscopy. Thirty-nine women had a laparoscopy after treatment and 56 women were followed up 12 months after treatment. INTERVENTIONS: Two high doses of dydrogesterone (either 40 or 60 mg) or a placebo, which was given for 12 days, beginning 2 days after the LH surge for a treatment period of 6 months. MAIN OUTCOME MEASURES: Change between before and after treatment endometriosis scores, pregnancy rates (PRs), and pain. RESULTS: Treatment with dydrogesterone did not alter the natural history of endometriosis or PRs when compared with placebo. Pain was reduced significantly during treatment with 60 mg dydrogesterone and this improvement still was evident at 12-month follow-up. CONCLUSION: Luteal phase dydrogesterone reduces pain associated with endometriosis.

3-dimensional reconstruction of ultrasound images of the uterine cavity.

We report our experience of 3-dimensional (3-D) reconstruction of ultrasound images of the uterine cavity. This is the first time that mapping of the contours of the uterine cavity with 3-D reconstruction has been achieved using standard clinical equipment for image acquisition. Ultrasound contrast hysterography was performed on 10 patients using both negative and positive intrauterine contrast media. 3-D image acquisition was performed during uterine cavity distension. The manipulation of the 3-D data sets is described and examples are shown. We believe that in some circumstances 3-D reconstructed images may be easier to interpret than 2-dimensional ultrasound images. We anticipate that this new technique will have a role in the preoperative assessment of uterine fibroids and endometrial polyps.

Ultrasound contrast hysterosalpingography--evaluation as an outpatient procedure.

Ultrasound contrast hysterosalpingography (HSG) uses intrauterine contrast media to increase the diagnostic value of plain transvaginal ultrasound enabling the uterine cavity contour to be assessed and allowing tubal patency to be determined. We present our experience using both negative (sterile saline) and positive (Echovist, Schering) contrast media in 27 patients presenting with a wide range of gynaecological disorders. This is the first report comparing the use of the two contrast media with plain ultrasound on a purely outpatient basis. We have found ultrasound saline HSG to be superior for the delineation of the uterine cavity and we predict that this will become a first line investigation for assessing the configuration of the uterine cavity. However, although Echovist could be demonstrated flowing through patent fallopian tubes, we found ultrasound contrast HSG to be insufficiently accurate in the determination of tubal patency and do not feel that it can replace conventional X-ray HSG. We review the literature on this technique and discuss its future role in gynaecological imaging.

Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy.

1. The time-course of the age-related decline in specific muscle force (maximum voluntary force per cross-sectional area) in men and women was determined by measuring the maximum voluntary force and cross-sectional area of the adductor pollicis muscle in 273 subjects aged 17-90 years (176 men, 30 premenopausal women and 67 peri- or post-menopausal women who were not receiving hormone replacement therapy). 2. To determine whether the loss of specific muscle force is hormone-dependent in women, we studied a further 25 women, aged 42-72 years, who were receiving hormone replacement therapy. 3. There was no significant difference in specific force between young men and pre-menopausal women. Around the time of the menopause there was a dramatic decline in specific force in women which was prevented by the use of hormone replacement therapy. In men the weakness started later (around the age of 60 years) and the decline in specific force was more gradual, reaching the level seen in post-menopausal women after the age of 75 years. 4. The protective effect of hormone replacement therapy on muscle strength is likely to be an important contributory factor to its proven action in preventing osteoporotic fractures. The dramatic peri-menopausal decline in muscle strength is a likely explanation for the known increases in falls and Colles' fractures around the time of the menopause.

25 mg oestradiol implants--the dosage of first choice for subcutaneous oestrogen replacement therapy?

OBJECTIVE: To assess the oestrogen concentrations and symptom relief obtained with 25 mg oestradiol implants. DESIGN: Open, observational study. SUBJECTS: Twelve symptomatic, post-menopausal women seen in a designated menopause clinic. INTERVENTION: A 25 mg oestradiol pellet was inserted subcutaneously, blood samples were obtained before implantation and at regular intervals (2-4 weeks) until symptoms refused as hypoestrogenaemia developed. MAIN OUTCOME MEASURES: Change in symptom score following implant treatment. Concentrations of oestrogens and their metabolites before and during low dose subcutaneous oestradiol therapy. RESULTS: Ten of the 12 women had excellent symptom relief, associated with oestradiol concentrations in the follicular range for between 28 and 35 weeks. The ratio of circulating oestrogen metabolites remained physiological, despite the oestradiol concentrations being substantially higher on treatment. CONCLUSIONS: We suggest that 25 mg pellets should be used as the initial dose for subcutaneous oestrogen treatment, and a combination of return of symptoms and weeks since insertion used to judge the timing of reimplantation.

Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.

Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone.

Sixteen postmenopausal women receiving conjugated equine oestrogens 1.25 mg/day, continuously, were randomly allocated to add dydrogesterone 20 mg/day for 12 days each calendar month for 3 months and then 10 mg/day in an identical fashion for a further 3 months, or to receive the dydrogesterone doses in reverse sequence. The effects of the two dydrogesterone doses on endometrial histology, vaginal bleeding, and the symptomatic and psychological status were compared. Endometrial samples were obtained around day 10 of progestogen addition. Dydrogesterone, 20 mg, induced uniform, late secretory transformation in all samples; with 10 mg one sample showed mixed early and late secretory features and another demonstrated late secretory changes associated with atypical hyperplasia. Both dydrogesterone doses induced an acceptable withdrawal bleed; most bleeding episodes were 'spotting' or normal in amount, and heavy bleeding was reported infrequently. There was one episode of breakthrough bleeding. There were no differences in bleeding patterns between the two dose regimens. Anxiety, and the physical and psychological status were significantly improved after 3 months of therapy. Significant benefits on depression were observed less clearly. There were no differences between the two dydrogesterone doses on anxiety, depression and the physical and psychological status, and, overall, the addition of the progestogen did not antagonize oestrogen benefits.

Effect on plasma lipids and lipoproteins of postmenopausal oestrogen therapy with added dydrogesterone.

In a prospective, randomized, cross-over study, 14 postmenopausal women completed 9 months of treatment with conjugated equine oestrogens, 1.25 mg daily. Seven women added dydrogesterone 20 mg daily for 12 days during months 2, 3 and 4, and then 10 mg daily for an identical time in months 5, 6 and 7. The other seven women added the two dydrogesterone doses in reverse sequence. No dydrogesterone was taken during months 8 and 9. Lipids and lipoproteins were measured before treatment and at the end of months 4, 7 and 9. Lipids were also estimated in an untreated (reference) group of eight postmenopausal women on two occasions 6 months apart; these showed significant changes in HDL2- and HDL3-cholesterol. In the treatment group, HDL-cholesterol and apolipoprotein (apo) A1 were significantly higher and LDL-cholesterol and apo B were significantly lower at months 4, 7 and 9 compared with baseline values. Triglyceride levels were increased significantly over baseline values, but remained within the normal range. No significant differences between the two dydrogesterone doses were observed on any lipid and lipoprotein fraction, nor were there any differences between the oestrogen-only and oestrogen/dydrogesterone treatment phases. Dydrogesterone appears to cause little, if any, lipid and lipoprotein changes and assessment in a larger population of postmenopausal women is warranted.

Oestriol with oestradiol verses oestradiol alone: a comparison of endometrial, symptomatic and psychological effects.

In a prospective, double-blind, randomized, cross-over trial, the effects of oral oestradiol, 2 mg daily, on the endometrial histology, frequency and severity of vaginal bleeding, and the symptomatic and psychological status of postmenopausal women were compared with those of oral oestradiol, 2 mg daily, plus oestriol, 1 mg daily. Both therapies were prescribed for 3 months on a cyclical basis. The addition of oestriol to oestradiol did not modify the endometrial response. The prevalence of proliferative/hyperplastic endometrium (64%: 9 of 14 biopsies) was similar after both treatments and there were no significant differences in either the frequency or heaviness of vaginal bleeding. Both therapies significantly reduced hot flushes, night sweats and vaginal dryness: no significant differences in effect on the symptomatic and psychological status were recorded. The addition of 1 mg of oestriol to 2 mg of oestradiol did not confer any benefit and the value of such an addition is challenged.

Is Provera the ideal progestogen for addition to postmenopausal estrogen therapy?

In a dose-ranging study, medroxyprogesterone acetate, 2.5, 5, or 10 mg daily, was given for 12 days of each calendar month to postmenopausal women also receiving conjugated estrogens, 0.625 mg daily, continuously. Endometrial biopsy specimens were taken on the sixth day of combined therapy for histologic, ultrastructural and biochemical evaluation. Medroxyprogesterone acetate induced secretory and ultrastructural changes within the endometrium, but the responses were variable and inconsistent. Suppression of epithelial deoxyribonucleic acid synthesis appeared dose-dependent. The levels of nuclear estradiol receptor, although reduced to within the secretory phase range, were not significantly lower than the values observed during the estrogen-only phase of treatment. Induction of both estradiol and isocitrate dehydrogenase activities was to within the secretory phase ranges, but the magnitude of these responses appeared less than those observed previously with other progestogens. Both morphologically and biochemically, medroxyprogesterone acetate, even at high dosage, produced suboptimal responses. Further studies are required to establish whether this is a dose-related effect.

Effects of dydrogesterone on the oestrogenized postmenopausal endometrium.

Postmenopausal women receiving conjugated oestrogens 1.25 mg daily continuously were also given dydrogesterone either 5, 10 or 20 mg daily for the first 12 days of each calendar month. Endometrial tissue obtained on the sixth day of combined therapy in the third or subsequent treatment cycle was subjected to histological, ultrastructural and biochemical assessments. Dydrogesterone provoked secretory histological and ultrastructural changes within the endometrium in a dose-dependent manner. A daily dose of 5 mg produced sub-optimal responses but 10 and 20 mg daily produced effects similar to those observed in the secretory phase of the ovulatory cycle. Dydrogesterone 10 mg and 20 mg daily reduced epithelial DNA synthesis and nuclear oestradiol receptor levels to values within the secretory phase range. A dose-response relation was seen in the induction of oestradiol-17 beta and isocitrate dehydrogenase activities; hyperphysiological values were observed with 20 mg of dydrogesterone daily. This study has demonstrated that dydrogesterone exerts potent anti-oestrogenic and progestational effects on the human endometrium which are dose-related. The 10 and 20 mg doses induced responses equal to or greater than those observed in the secretory phase of the ovulatory cycle and both dosages can be recommended for use in combination with exogenous oestrogens in postmenopausal women: and they may also have a role in the management of anovulatory dysfunctional uterine bleeding.

How progestins prevent endometrial cancer.

This article discusses the role of progestational hormones in cancer of the endometrium in menopausal women and indicates the type of progestin and the doses which appear necessary to prevent anomalies of the endometrium. It is in fact established that the incidence of endometrial adenocarcinomas is augmented by the application of a continuous oestrogenic without countervailing progestational-stimulus. Progestogens have an antimitotic action on endometrial cells, which leads to reduction of the oestrogenic stimulus and the probability of the occurrence of tissue anomalies. However, it is probable, and theoretically possible, that the regular disintegration of the endometrium may be capable of removing the potentially anomalous cells before they develop into carcinomas. Any oestrogenic treatment, however, whatever the dose and mode of administration, is not more certain than any other. The association of a progestogen is necessary but the choice of the individual progestogen is dictated by custom or fashion. It seems that administration during 12 days per month in a manner designed to obtain rhythmic bleedings may be the best solution.

Steroid hormone receptors in the female lower urinary tract.

The preliminary results of a study to estimate the level of cytosol oestrogen and progesterone receptors in the lower urinary tract are presented. 29 full thickness biopsies were obtained from the vault, trigone and urethra of 9 female surgical patients aged 13-72 years. Cytosol assay for oestradiol-17 beta receptors and progesterone receptors was performed. Oestrogen receptors were present in all 5 urethral specimens examined and with a consistently higher concentration in the middle and distal thirds in comparison to the proximal urethra. In only 1 of the 9 vault specimens and 8 trigone specimens were receptors found and those in small quantities. No progesterone receptors were determined in any of the vault, trigone and urethral specimens examined. The presence of oestrogen receptors in the middle and distal thirds of the human female urethra is strong supportive evidence of the sensitivity of the urethra to oestrogens, and the higher concentration of those receptors in these sites in comparison to the proximal urethra, vault and trigone confirms the common embryological origin of the distal urethra and vagina from the definitive urogenital sinus. The absence of measurable progesterone receptors in all the lower urinary tract specimens examined is discussed.

Simple biochemical method to assess progestin effects on human endometrial DNA synthesis and its application to endometrial carcinoma.

Endometria of normal histology from postmenopausal women receiving either estrogen or estrogen plus a progestin have been analyzed for nuclear estradiol receptor, epithelial DNA synthesis, isocitric dehydrogenase, and estradiol dehydrogenase activities. Epithelial DNA synthesis correlated positively with nuclear estradiol receptor and negatively with both the dehydrogenases; this result was obtained regardless of whether the enzyme activity was related to the protein or DNA content of the samples. Thus, either of the dehydrogenases might provide an index of progestin effects on proliferative activity in endometrial carcinomata. Provera administered in vivo had no effect on either dehydrogenase activity in soluble estradiol receptor-poor carcinomata, whereas both dehydrogenase activities were high in some but not all soluble estradiol receptor-rich tumors. The enzyme activities in Provera-treated tumors have been compared with those in normal epithelium and endometrium from postmenopausal women taking estrogen plus progestin. The activities of both dehydrogenases were lower in soluble estradiol receptor-rich carcinomata than in either endometrium or epithelium from estrogen plus progestin-primed, normal postmenopausal women. This may indicate suboptimal progestin effects in the patients with carcinoma, and potential reasons for this are discussed.

Dose dependent effects of oral progesterone on the oestrogenised postmenopausal endometrium.

Oral progesterone 100, 200, or 300 mg daily was given for the first 10 days of each calendar month to postmenopausal women also receiving conjugated oestrogens 1.25 mg daily continuously. Endometrial biopsy specimens were taken on the sixth day of the third or subsequent cycle of combined treatment for histological, ultrastructural, and biochemical evaluation. Secretory histological changes were induced within the endometrium in a dose dependent manner, as were progesterone sensitive ultrastructural features such as nucleolar channel systems, giant mitochondria, and subnuclear accumulations of glycogen. Dose response relations were also observed for suppression of DNA synthesis and nuclear oestrogen receptor, and for induction of the activities of oestradiol and isocitric dehydrogenases. Progesterone administered by mouth clearly provokes an end organ response within the endometrium. Suboptimal effects were observed with the lower doses but progesterone 300 mg daily achieved responses approaching and within the physiological range. This dose may therefore be effective as an alternative to synthetic progestogens for therapeutic purposes.

A controlled trial of naproxen sodium for relief of pain associated with Vabra suction curettage.

In a double-blind study naproxen sodium (550 mg), or placebo was administered 1 h before Vabra curettage and pain associated with the procedure was assessed immediately after operation and 30, 60 and 120 min later by visual analogue and verbal rating scales, and the McGill pain questionnaire. The pre-curettage anxiety of the patients was assessed by the Spielberger state anxiety inventory. Of the 58 patients, 51 (87.9%) reported pain during the procedure; there was no relation between the level of pain experienced and the pre-curettage anxiety score. Compared with the placebo group, the pain experienced by the naproxen group was significantly less as measured by the McGill pain questionnaire immediately after curettage, and by visual analogue scales 30 and 60 min after the procedure. The verbal rating scales showed that naproxen significantly reduced backache 30 min after curettage, and cramp immediately after the procedure and 30 and 60 min later but did not reduce the severity of the pain associated with the procedure.

Dose-dependent effects of synthetic progestins on the biochemistry of the estrogenized post-menopausal endometrium.

Symptomatic post-menopausal women were treated with conjugated equine estrogens (Premarin; Ayerst International) 1.25 mg daily, continuously, adding either norethisterone (Primolut N; Schering Chemicals) 1, 2.5, 5 or 10 mg daily or D/L norgestrel (Wyeth Laboratories) 150 or 500 micrograms daily for 10 days each calendar month. Endometrial biopsies were obtained during estrogen therapy alone and on the 6th day of combined estrogen/progestin administration. Sensitive biochemical indices of estrogen and progestogenic activities were measured in th endometrial samples. These included measurements of DNA synthesis in epithelium and stroma by tritiated thymidine autoradiography; nuclear estradiol receptor content, and the activities of estradiol 17 beta and isocitric dehydrogenase and acid and alkaline phosphatase. Low dosages of progestins achieved maximal biochemical effects and the larger doses failed to enhance these responses. It is concluded that the dosages of progestins currently added in post-menopausal estrogen therapy are greatly in excess of those necessary to suppress endometrial proliferation effectively; lowering the daily progestin dosage is unlikely to result in any lessening of this protective effect and will probably reduce the incidence of side effects, as these appear to be dose-dependent.