Alfred N. Poindexter

Epidemiology of endometriosis among parous women

Objective To report the prevalence of endometriosis and its associated risk factors among multiparous women, and to determine the relationship between the location and depth of this disease and certain medical and behavioral characteristics. Methods Over a 6-year period, 3384 multiparous women underwent laparoscopy for tubal sterilization. Endometriosis was detected in 126 patients (3.7%), who were consequently evaluated for severity of the disease. To conduct a casecontrol study, 504 patients with no evidence of endometriosis were randomly selected from a group of women who underwent sterilization. Information obtained through physical examination and a self-administered questionnaire was studied by multivariate logistic regression analysis. Results Most endometriosis lesions were minimal. Factors associated with an increased risk for endometriosis included: advanced age (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.1–3.7), Asian race (OR 8.6, 95% CI 1.4–20.1), long cycle length (OR 1.8,95% CI 1.1–2.7), one live birth (OR 2.2, 95% CI 1.1–4.3), long duration of intrauterine device use (OR 3.0, 95% CI 1.1–8.1), and long duration of uninterrupted menstrual cycles (OR 2.9, 95% CI 1.3–6.4). Present oral contraceptive use was protective for disease (OR 0.5, 95% CI 0.2–0.9). The role of these factors varied among different disease locations (ovary, uterus and tubes, posterior broad ligaments and cul-de-sac), and depth (superficial or deep). Conclusions The prevalence of endometriosis is relatively low among multiparous women, and certain menstrual and reproductive characteristics are associated with its development. Furthermore, the relationship between various factors and endometriosis appears to be site and depth specific. Our findings suggest that asymptomatic endometriosis may be clinically important.

Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle

Recent studies suggest that the progesterone receptor isoforms (PR-A and PR-B) activate genes differentially and that PR-A may act as a repressor of PR-B function. Hence, the absolute and relative expression of the two isoforms will determine the response to progesterone. We have measured their relative expression in the uterus of cycling women who underwent endometrial biopsy. PR isoforms were identified on blots of SDS-PAGE gels by reaction with the AB-52 antibody after immunoprecipitation from endometrial extract. Both isoforms were highest in the peri-ovulatory phase, but levels of PR-A were always higher than those of PR-B. The ratio of PR-A to PR-B changed during the menstrual cycle. Between days 2 and 8, PR-B is almost undetectable and the A:B ratio is >10:1. From days 9 to 13, the ratio is about 5:1, and it is about 2:1 between days 14 and 16. Thereafter, PR-B dwindles rapidly and is virtually undetectable at the end of the cycle. In various hypoestrogenic environments, PR-B expression was reduced. However, exogenous estrogens in the follicular phase in the form of oral contraceptives, enhanced PR-B expression. These data support the possibility that progesterone acts through cycle-specific PR isoforms.

Experiences of injectable contraceptive users in an urban setting

Objective To examine method-related experiences and acceptability of depot medroxyprogesterone acetate (DMPA) among women using this contraceptive for the first time. Methods Five hundred thirty-six women who received an injection of DMPA from any of seventeen clinical settings in southeast Texas, United States, were followed for 1 year. At each follow-up visit, patients were asked about their experiences with DMPA during the past 3 months and their plans to use this method in the future. Results Amenorrhea, irregular bleeding, and weight gain were the conditions reported most frequently. Reports of amenorrhea, weight gain, and acne or skin problems increased over time, but complaints of longer periods decreased (P <.001). Two pregnancies occurred during the study period. However, of these, one existed before the first injection. Depot medroxyprogesterone acetates continuation rate at 1 year was 28.6%. Heavier and more frequent bleeding, increased cramping, amenorrhea, weight gain, headaches, depression, and nervousness were more frequent complaints of women who discontinued DMPA (P <.05), whereas lighter and less frequent bleeding were reported more often by those who continued to use this method (P <.05). Women who discontinued use of DMPA were more likely to be married and have a concern about injectable contraceptives than those who continued to use this method. Conclusion Intolerable side effects and changes in menstrual pattern are the most frequently indicated reasons for discontinuing DMPA use. Our results suggest that DMPAs 1-year continuation rate may be lower than previously reported.

A multi-compartment, single and multiple dose pharmacokinetic study of the vaginal candidate microbicide 1% tenofovir gel

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496

High doses of oral contraceptives do not alter endometrial α1 and αvβ3 integrins in the late implantation window

Objective To assess the effects of an emergency contraceptive agent on the distribution of integrin heterodimers during that part of the implantation window. Design Prospective, case-controlled study in a university-based Population Program. In the first ovulatory control cycle after the detection of LH surge, patients had endometrial sampling 11 days after the surge. In the next cycle the procedure was repeated 2 days after the administration of a postcoital contraceptive agent on day 9 after LH surge (100 g ethinyl E 2 and 2mg norgestrel). Main Outcome Measures The effects of postcoital contraceptives on the expression of integrin heterodimers ( α 1 and α v β 3 subunits) reported to be unique to secretory phase was determined. Results All six specimens were consistent histologically with days 24 and 25 of the menstrual cycle by light microscopy. Using immunohistochemistry, strong membrane staining of endometrial glandular cells and superficial epithelium for both α 1 subunit and vitronectin ( α v β 3) receptor was observed in treatment and controls. No diminution of intensity or distribution was observed relative to pretreatment controls. Conclusions There is no apparent change in the level of these two integrins in the human endometrium when high-dose oral contraceptives are given in the later stages of the implantation window. This suggests that the high doses of steroids used in emergency contraceptives may exert their effect through more complex mechanisms than endometrial cell surface changes.

One-year experience with subdermal contraceptive implants in the United States

Women who received Norplant contraceptive implants from any of fifteen clinical settings in southeast Texas, U.S.A., were followed for one year to determine their reactions to the method. Of 1,385 who enrolled to receive Norplant implants, 1,253 had implants inserted. Side effects were reported by 78% of those receiving implants and 70% described changes in bleeding patterns. Spotting or irregular bleeding, weight gain and headaches were the conditions reported most frequently. Nine pregnancies were reported during the study period. Six of these, however, existed before the implants were inserted. At the one year anniversary, 143 of women receiving implants had had them removed. Those who discontinued method use were less satisfied, reported more side effects and were more likely to have planned to have another child, thus using the method for spacing, or to have had a change in their marital status while they were using the contraceptive. Providers should counsel patients to focus attention on plans for the future in selecting their contraceptive method. In addition, we recommend, as does the products distributor, that providers confirm that patients are not pregnant prior to inserting implants.

Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men.

Objectives: To assess safety and acceptability of penile application of BufferGel (ReProtect, Baltimore, MD) and PRO 2000 Gel (Indevus Pharmaceuticals, Lexington, MA)compared with placebo among low‐risk sexually abstinent men and HIV‐positive sexually abstinent men. Design: Seventy‐two healthy low‐risk men (36 uncircumcised) and 25 HIV‐positive men (12 uncircumcised) were enrolled in 3 double‐blind, single‐center studies as follows: 36 low‐risk men in a study of BufferGel and K‐Y Jelly (McNeil‐PPC, Skillman, NJ) placebo; 36 low‐risk men in a study of PRO 2000 Gel and vehicle placebo; and 25 HIV‐positive men in a crossover study of BufferGel, PRO 2000 Gel, and K‐Y Jelly placebo. Methods: Participants applied product to the penis on 7 consecutive nights, kept study diaries, and were then interviewed and examined. Urine was tested for inflammation by leukocyte esterase. Results: No serious adverse events (AEs) or urethral inflammation was detected. During use of BufferGel, 3 low‐risk men (13%) reported 6 AEs and 2 HIV‐positive men (8%) reported 3 AEs. During use of PRO 2000 Gel, 4 low‐risk men (17%) reported 6 AEs and 1 HIV‐positive participant (4%) had 1 AE. AE rates during use of BufferGel and PRO 2000 Gel use were not significantly different from rates observed during placebo. One low‐risk man (4%) would object to his partners using BufferGel and 3 (13%) to PRO 2000 Gel. Two HIV‐positive men (8%) reported they would object to partners using either BufferGel or PRO 2000 Gel. Conclusions: Daily application of BufferGel and PRO 2000 Gel directly to the penis consecutively for 7 days was generally safe and well tolerated among healthy low‐risk men and HIV‐positive men. These microbicides have acceptable safety profiles to proceed with planned phase 3 vaginal microbicide trials.

Comparative crossover study of the PATH Woman's Condom and the FC Female Condom®

BACKGROUND Only one female condom [FC1 Female Condom (FC1)] is currently marketed, but it is poorly utilized, perhaps due to difficulty with insertion, discomfort and suboptimal functional performance during intercourse. The Program for Appropriate Technology in Health (PATH) Womans Condom (WC) was developed in an effort to overcome these obstacles. STUDY DESIGN This was a randomized crossover study to evaluate the functional performance, safety and acceptability of the FC1 and WC. Seventy-five couples were assigned to one of two condom use sequences (WC/FC1 or FC1/WC) at three centers. Four condoms of the first type were used by couples in four acts of intercourse at home over a 2-4-week period. After a follow-up visit, these procedures were repeated with the second assigned condom type. In a substudy of participants (n=25), a colposcopy was performed prior and subsequent to the first condom use of each of the two condom types. Condom performance was evaluated by calculating measures of function from questionnaires completed by the couple after each condom use. Safety was evaluated by reported urogenital symptoms with a given condom during or immediately following condom use and colposcopic signs of genital irritation in the substudy. Acceptability of each given condom type was measured by questionnaire. RESULTS Total condom failure (slippage, breakage, etc., divided by the number of female condoms opened) was 31% for the WC and 42% for the FC1. Total clinical failure (slippage, breakage, etc., divided by the number of female condoms used) was 17% for the WC and 24% for the FC1. The proportion of condom failures was 10.9 percentage points less, and the proportion of clinical failure 6.7 percentage points less, when couples used the WC compared to the FC1 [90% CI: -18.5 to -3.3 and -12.6 to -0.8, respectively). Fewer women reported symptoms of urogenital irritation when using the WC vs. the FC1 either overall or when analyzing each use of the condom [woman as unit: -20 percentage points (90% CI: -30.5 to -9.3); condom use as unit: -12.3 percentage points (90% CI: -18.0 to -6.7)]. A similar result was seen for signs of urogenital irritation [woman as unit: -20 percentage points (90% CI: -42.7 to 4.8)]. Among participants with a preference, WC was preferred over the FC1 by twice as many males and by 2.6 times as many females. CONCLUSIONS While both female condoms were safe and acceptable in short-term use, the PATH Womans Condom leads to less failure, was associated with fewer adverse events, and was more acceptable than the FC1 Female Condom.

Factors associated with unintended pregnancy

This research was designed to identify determinants of unintendedpregnancy among women attending family practice or family planning clinics.Survey data were collected from 95 women who were categorized according towhether or not they had experienced an unintended pregnancy. Women reportingunintended pregnancy were younger, reported earlier sexual debut and agreater number of sexual partners than those not having experienced anunintended pregnancy. Those who had avoided unintended pregnancy displayedhigher levels of preventive sexual self-efficacy, had more confidence intheir ability to use contraceptive methods, perceived more negativeconsequences associated with having children in the near future, andbelieved pregnancy among unmarried women to be less acceptable than didwomen who had had unintended pregnancies.

Characteristics and attitudes of early contraceptive implant acceptors in Texas.

In 1991, shortly after Norplant became available in the United States, 678 women who had received the implant from 17 providers in Texas were surveyed. Forty-five percent of these women were under 21 years old. The majority (56%) had tried the implant because they were dissatisfied with their previous contraceptive method. Forty-four percent of the sample indicated that the implant was one of the first contraceptive methods they had used and that they had only recently decided to prevent unplanned pregnancy. The average number of children per woman was 1.2, and one-third of the sample had had at least one abortion. While 37% of the women said they wanted no more children, 63% said they were using the implant as a spacing method. The reasons for choosing the implant and concerns about it varied according to the users age, educational level and race or ethnic group.