David L. Hemsell

Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer

The purpose of this study was to ascertain if a relationship exists between the transfer constant of conversion of plasma androstenedione to estrone ([rho]AE1BU) and total body weight or excessive body weight in 50 postmenopausal women, of whom 25 had adenocarcinoma of the endometrium and 25 had no endometrial disease. The [rho]AE1BU ranged from 0.015 to 0.129 in these 50 women. The [rho]AE1BU in the women with endometrial cancer was 0.051 +/- 0.006 (mean +/- S.E.), whereas that in the women with no endometrial disease was 0.039 +/- 0.004. These values are not significantly different (p greater than 0.05). The body weights of these 50 women ranged from 104 to 430 pounds. The weight of the patients with endometrial cancer was 234 +/- 16 pounds (mean +/- S.E.), and that for the women with no endometrial disease was 194 +/- 12 pounds. A statistically significant correlation (p less than 0.001) was found between [rho]AE1BU and body weight and between [rho]AE1BU and excessive body weight in both groups of women. Moreover, obesity and aging appear to act in concert to potentiate the conversion of plasma androstenedione to estrone in extraglandular sites since the [rho]AE1BU is considerably greater among obese postmenopausal women than among comparably obese premenopausal women.

Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome.

Abstract A family with incomplete male pseudohermaphroditism inherited as an apparent X-linked recessive trait was investigated. The phenotype in 11 affected family members ranged from a minimal de...

Massive Extraglandular Aromatization of Plasma Androstenedione Resulting in Feminization of a Prepubertal Boy

This report describes the mechanism of origin and the quantity of estrogen produced in a prepubertal boy who developed severe feminization at 8 yr of age as the result of a heretofore undescribed metabolic abnormality. The clinical findings were gynecomastia and accelerated linear growth and bone maturation. At the time feminization developed, there were no signs of growth or development of the otherwise normal prepubertal male external genitalia or any increase of muscle mass that normally accompanies male puberty. The hyperestrogenism was found to be the consequence of massive extraglandular conversion of plasma androstenedione to estrone. During a 6-mo period of study, the plasma production rate of androstenedione ranged from 1.2 to 1.6 mg/day. More than 55% of plasma androstenedione was metabolized by aromatization to estrone which, in turn, was extensively sulfurylated in the tissue sites of aromatization before its entry into the blood. Thus, estrone sulfate was the final product in the aromatizing sites, and the plasma production rate of estrone sulfate derived from plasma androstenedione was 782 mug/24 h. The extent of extraglandular conversion of plasma androstenedione to estrone measured in this boy was 50 times that observed in two normal prepubertal boys. Moreover, 94% of the extraglandular aromatization occurred in extrahepatic sites. The metabolic clearance rate of plasma androstenedione, 2,380 liters/day per m(2), was markedly increased in this boy. Approximately 1,500 liters of plasma androstenedione clearance was accounted for by extrahepatic, extraglandular aromatization. The fractional conversion of testosterone to estradiol, 0.16, was 50 times greater in this boy than that observed in normal young adult men. The total extent of aromatization of plasma prehormones was even greater in this boy inasmuch as evidence was obtained that aromatization of 16-hydroxysteroids, e.g. 16alpha-hydroxy androstenedione and 16alpha-hydroxy dehydroisoandrosterone (sulfate), resulted in estriol formation independent of estrone formation. Thus, extensive extrahepatic, extraglandular aromatization resulted in advanced feminization in this prepubertal boy by a previously undescribed metabolic abnormality.

NAD+-dependent 15-hydroxyprostaglandin dehydrogenase activity in human endometrium.

The specific activity of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase was measured in human endometrial tissue obtained from ovulatory and anovulatory women. Employing PGE2 as substrate, the specific activity of this enzyme was found to be highest in endometrial tissue during the secretory phase of the cycle (ovarian cycle days 15-25) and lowest in menstrual (days 1-5) and premenstrual (days 26-28) endometrium. The specific activity of prostaglandin dehydrogenase in endometrium of anovulatory women was low, being similar to that found in proliferative endometrium (days 6-14) of ovulatory women. Prostaglandin dehydrogenase activity was found in the cytosolic fraction prepared from endometrial ti-sue, and was found principally in the glandular epithelium following separation of endometrial glands and stromal cells.

Design of the PID Evaluation and Clinical Health (PEACH) Study

This paper describes the PID Evaluation and Clinical Health Study (PEACH), a multicenter, randomized clinical trial designed to compare treatment with outpatient and inpatient antimicrobial regimens among women with pelvic inflammatory disease (PID). PEACH is the first trial to evaluate the effectiveness and cost-effectiveness of currently recommended antibiotic combinations in preventing infertility, ectopic pregnancy, chronic pelvic pain, recurrent PID, and other health outcomes. It is also the largest prospective study of PID ever conducted in North America. We describe the PEACH studys specific aims, study organization, patient selection criteria, conditions for exclusion, data collected upon entry, randomization and treatment, adherence measures, follow-up activities, quality-of-life measures, outcomes, and statistical analyses. In the first 11 months of enrollment (March 1996-January 1997), 312 women were randomized. Of eligible women, 59% consented to enroll. Participating women are primarily black (72%) and young (mean age 24 years). After a median of 5.5 months of follow-up, we were in contact with 95% of study participants. The PEACH study will provide a rationale for selecting between inpatient and outpatient antibiotic treatment, the two most common treatment strategies, for PID.

Fallopian tube prolapse after hysterectomy

BACKGROUND Fallopian tube prolapse is reported to most commonly occur after vaginal hysterectomy. Both diagnosis and management have varied, resulting in differing efficacies of treatment. METHODS We reviewed the presentation, diagnosis, management, and outcomes of 18 cases of tubal prolapse in 17 women. RESULTS Most cases (65%) occurred after abdominal hysterectomy. The post-hysterectomy course was complicated by cuff cellulitis in three women, an infected cuff hematoma in one, and post-extubation pulmonary edema in one; four were observed for elevated temperature only. At presentation, 44% complained of dyspareunia, 39% vaginal bleeding, 33% vaginal discharge, 28% abdominal pain, and 28% were asymptomatic. Seven women had vaginal excision (one requiring an additional abdominal procedure), three had laparotomy with salpingectomy, and seven (41%) had spontaneous disappearance of prolapsed fallopian tube without treatment. CONCLUSIONS In our series, tubal prolapse most commonly occurred after abdominal hysterectomy. Moreover, women with tubal prolapse may be asymptomatic, and observation alone may lead to resolution.

Multicenter comparison of cefotetan and cefoxitin in the treatment of acute obstetric and gynecologic infections

Two hundred eighty-seven women were treated in a multicenter, randomized, comparative study to compare the safety and efficacy of cefotetan every 12 hours with that of cefoxitin every 6 or 8 hours in the treatment of acute obstetric and gynecologic pelvic infections. The most frequent primary diagnoses in both groups were endometritis and pelvic inflammatory disease; 24 of these patients were also bacteremic. The mean duration of treatment was 5.2 and 5.4 days for the cefotetan and cefoxitin groups, respectively, and the total doses administered were 18.1 and 32.1 gm, respectively. The rate of clinical failure for the cefotetan group was 8.5% and 12.2% for the cefoxitin group. Laboratory and clinical adverse reactions were infrequent and none was serious; both antimicrobials were well tolerated. These results suggest the administration of cefotetan provided adequate clinical and bacteriologic effectiveness in the treatment of hospital- and community-acquired, polymicrobial obstetric and gynecologic pelvic infections.

Preventing major operative site infection after radical abdominal hysterectomy and pelvic lymphadenectomy

Twenty-one women who underwent radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled in a prospective, comparative, randomized, placebo-controlled clinical trial of antimicrobial prophylaxis. Preoperative endocervical flora was identified and was similar in pre- and postmenopausal private and clinic service women; 46% of the 119 preoperative isolates produced beta-lactamase enzyme. Women were given three doses of either placebo or cefoperazone plus sulbactam, an irreversible beta-lactamase enzyme inhibitor. Three women (27%) given placebo developed abdominal incision infections; one women given placebo also developed a pelvic infection. None given antibiotic developed operative site infection, but one women developed a drain site infection. A major operative site infection rate of 27% observed with placebo is high enough to warrant prophylaxis. Although antimicrobial prophylaxis at radical hysterectomy and pelvic lymphadenectomy eradicted operative site infection in our patient populations, a literature review indicates that individual determination of a requirement for prophylaxis is necessary.

Oral trovafloxacin compared with intravenous cefoxitin in the prevention of bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease

BACKGROUND Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective hysterectomy. METHODS In a randomized, double-blind, multicenter study, parallel groups of women 18 years of age or older received either 200 mg trovafloxacin by mouth and intravenous (i.v.) placebo or 2 g cefoxitin by i.v. infusion and placebo by mouth before elective vaginal or abdominal hysterectomy for nonmalignant disease. RESULTS In the 103 and 97 patients in the trovafloxacin and cefoxitin groups, respectively, who were evaluable for efficacy, the prophylactic success rates at hospital discharge (96% in both groups) and 30 +/- 6 days after hysterectomy (88% and 91% in the trovafloxacin and cefoxitin groups, respectively) were statistically equivalent. Both antibiotics were well tolerated. CONCLUSION A single oral 200 mg dose of trovafloxacin is as effective and safe as a standard cefoxitin parenteral regimen in the prevention of primary bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease.

Abdominal Wound Problems After Hysterectomy With Electrocautery vs. Scalpel Subcutaneous Incision

The purpose of this study was to evaluate the relationship between postoperative abdominal incision problems and opening subcutaneous tissues with electrocautery or scalpel. Women scheduled for elective abdominal hysterectomy who gave informed consent were randomly assigned to subcutaneous abdominal wall tissue incision by electrocautery or scalpel. Postoperative abdominal wound problem diagnoses included seroma, hematoma, infection, or dehiscence without identifiable etiology. Fifteen of 380 women (3.9%) developed a wound problem; six had scalpel and nine had electrosurgical subcutaneous incisions (P = 0.4). Thicker subcutaneous tissues (P = 0.04) and concurrent pelvic infection (P < 0.001) were significant risk factors for postoperative wound problems. Only two women (0.5%) developed an infection. We conclude that the method of subcutaneous tissue incision was unrelated to the development of postoperative abdominal incision problems in 380 women undergoing elective abdominal hysterectomy.