Hormonal and barrier contraception and risk of upper genital tract disease in the PID Evaluation and Clinical Health (PEACH) study.

OBJECTIVE: Among women diagnosed with pelvic inflammatory disease, we examined the associations between hormonal or barrier methods of contraception and upper genital tract infection or inflammation. METHODS: Participants were 563 patients from a treatment trial for pelvic inflammatory disease. All had pelvic pain; pelvic organ tenderness; and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Contraceptive use within the prior 4 weeks was compared among women with baseline upper genital tract gonorrhea or chlamydia, women with endometritis without upper genital tract gonorrhea or chlamydia, and women with neither upper genital tract gonorrhea or chlamydia nor endometritis. RESULTS: Inconsistent condom use was significantly and independently associated with a 2 to 3 times elevated risk for upper genital tract infection. Upper genital tract gonorrhea or chlamydia was not significantly associated with use of oral contraceptives, use of medroxyprogesterone, condoms used consistently, nor other barrier methods. CONCLUSION: No hormonal or barrier contraceptive method was related to a reduction in upper genital tract disease among women with clinical pelvic inflammatory diseases.

Douching and endometritis: results from the PID evaluation and clinical health (PEACH) study.

BACKGROUND: Douching has been related to risk of pelvic inflammatory disease (PID). GOAL: To examine the association between douching and PID in a large, multicenter, clinical trial of PID after adjustment for race/ethnicity. STUDY DESIGN: Interviews were conducted with 654 women who had signs and symptoms of PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained from all the women. Women with evidence of plasma cell endometritis and/or gonococcal or chlamydial upper genital tract infections were compared with women who had neither endometritis nor upper genital tract infection. RESULTS: Women with endometritis or upper genital tract infection were more likely to have douched more than once a month or within 6 days of enrollment than women who never douched. These associations remained after adjustment for confounding factors, after analysis of black women only; and among women with normal or intermediate vaginal flora but not bacterial vaginosis. CONCLUSION: Among a predominantly black group of women with clinical PID, frequent and recent douching was associated with endometritis and upper genital tract infection.

Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease.

OBJECTIVE: Careful detection and treatment of pelvic inflammatory disease are essential for the prevention of adverse sequelae. The purpose of this study was to evaluate the diagnostic test characteristics of clinical criteria for the diagnosis of pelvic inflammatory disease. STUDY DESIGN: We performed a cross-sectional analysis of the baseline characteristics of 651 patients enrolled in a multicenter randomized treatment trial for pelvic inflammatory disease. Clinical and laboratory findings were recorded for all patients, and endometrial sampling was performed. We calculated sensitivity and specificity and performed receiver operating characteristic curve analysis and multivariate logistic regression, using histologic endometritis as the criterion standard. RESULTS: The minimal criteria for pelvic inflammatory disease, as recommended by the Centers for Disease Control and Prevention, had a sensitivity of 83%, in comparison with a 95% sensitivity for adnexal tenderness (P =.001). Of the supportive clinical criteria, the finding most highly associated with endometritis was a positive test result for Chlamydia trachomatis or Neisseria gonorrhoeae (adjusted odds ratio, 4.3; 95% confidence interval, 2.89--6.63). A multivariate logistic regression model indicated that combinations of criteria significantly improve the prediction of endometritis. CONCLUSION: Sensitivity can be maximized by using the presence of adnexal tenderness as a minimal criterion for the diagnosis of pelvic inflammatory disease, and supportive criteria are helpful in estimating the probability of endometritis.

Torsion of the uterine adnexa. Pathologic correlations and current management trends.

OBJECTIVE: To evaluate the clinical and pathologic correlates of specimens removed for the diagnosis of adnexal torsion and to evaluate trends in the management of torsion. STUDY DESIGN: Cases of ovarian or adnexal torsion (N = 104) were identified retrospectively over a period extending from January 1987 to March 1998 by the coding of ovarian, fallopian tube or adnexal torsion. Statistical evaluation was by chi 2 analysis using the Bonferroni inequality correction when appropriate. RESULTS: Neoplastic and functional tumors of the ovary composed > 90% of the diagnoses at microscopic evaluation, with cancer diagnosed in < 1% of cases. Laparoscopy was attempted in 47 (46%) cases, and adnexasparing procedures were performed in 20 (19%) patients. Patients treated in the latter half of the study were not less likely to undergo laparotomy than those treated in the first half; however, conversion from laparoscopy to laparotomy was significantly less common in the latter half. Patients in this study were more likely to receive an adnexa-sparing operation than historical controls, but there was no improvement in this rate from the first to the second half of this study. A history of previous abdominal surgery was the most common associated condition, but 47% of patients had no known risk factors. Ovarian hyperstimulation, previously omitted in series reports, was an antecedent factor in 9% of patients. CONCLUSIONS: Adnexal torsion is most commonly associated with a benign process. A more-conservative approach to the treatment of this process is becoming increasingly common, as seems warranted in light of the low incidence of malignancy. The need for conversion from a laparoscopic to an open approach appears to have been waning over the last decade; that may correlate with an increased comfort level in gynecologists with laparoscopic approaches.

Predictors of response to sertraline treatment of severe premenstrual syndromes.

BACKGROUND: Serotonergic antidepressant medications have demonstrated efficacy in the treatment of severe premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Over 60% of subjects responded well to sertraline treatment for PMS and PMDD in double-blind controlled studies. However, no studies have evaluated the predictors of treatment response for this disorder. The current study examined pretreatment demographic, medical history, and clinical symptom predictors of sertraline response in PMS and PMDD treatment. METHOD: Sixty-two subjects diagnosed with severe PMS (according to the Daily Symptom Report and global ratings of functional impairment) or PMDD (DSM-IV) received sertraline treatment as part of a randomized, double-blind, placebo-controlled treatment efficacy study. All subjects completed 3 screening cycles, including a single-blind placebo washout cycle, prior to 3 cycles of double-blind treatment. Outcome was assessed across the domains of PMS symptoms and quality of life. Demographic, medical history, and symptom variables were used to predict sertraline response. RESULTS: Baseline postmenstrual symptom ratings were significantly and independently associated with posttreatment PMS symptoms in multivariate analysis. Premenstrual and postmenstrual ratings of depression, medical history variables, and demographic variables were not significantly predictive of response to sertraline. CONCLUSION: Baseline postmenstrual symptom ratings controlled for baseline premenstrual symptoms were associated with PMS symptoms at sertraline treatment endpoint. The findings suggest that nonmenstrual-related baseline characteristics other than depression may influence sertraline treatment outcome in patients with higher postmenstrual symptom levels.

Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial.

BACKGROUND: Studies show that selective serotonin reuptake inhibitors are effective for severe premenstrual syndrome and premenstrual dysphoric disorder. This study compares the efficacy of a selective serotonin reuptake inhibitor with that of a tricyclic antidepressant to determine whether efficacy for premenstrual syndrome/premenstrual dysphoric disorder is a general or more serotonergic effect of antidepressants. METHODS: After 3 screening months, 189 subjects were randomized to sertraline hydrochloride, desipramine hydrochloride, or placebo for 3 months of double-blind treatment. The flexible dosage range was 50 to 150 mg/d. The outcome measures included the Penn Daily Symptom Report (DSR), the Hamilton Depression Rating Scale, the Clinical Global Impressions-Severity Scale, the Quality of Life Scale, and Patient Global Ratings of Functioning and Improvement. Analyses included all subjects with treatment data, with the last observation carried forward. RESULTS: Sertraline was significantly more effective than placebo or desipramine; desipramine was not better than placebo (F2,163 = 12.47, P<.001). All DSR factors were more improved with sertraline compared with desipramine and placebo; the factors for mood (P<.001) and pain (P = .05) were significant, and the results of all outcome measures were consistent. A history of depression, postmenstrual symptom levels, and other diagnostic variables added individually as covariates did not alter the treatment results. At end point analysis, DSR symptoms had decreased by more than 50% in 40 subjects (65%) in the sertraline group, 18 subjects (36%) in the desipramine group, and 16 subjects (29%) in the placebo group (P<.001). CONCLUSIONS: The comparison of 2 classes of antidepressants strongly favored the serotonergic drug, which effectively reduced symptoms and improved functioning and was well tolerated by women with severe premenstrual syndrome. A history of depression did not alter the treatment results.

Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant.

Evidence that serotonergic antidepressants are effective for treating premenstrual syndrome (PMS) raises the question of whether dosing only in the symptomatic premenstrual phase is effective for this disorder. This preliminary randomized, double-blind study compared the responses to half-cycle or full-cycle dosing of sertraline in 31 patients who completed a preceding double-blind, short-term treatment trial. The subjects fulfilled criteria for severe PMS when they entered the preceding controlled trial. At the end of the short-term treatment trial, the double-blind was not broken; both improved and unimproved subjects were randomized in a double-blind fashion to receive either full-cycle or half-cycle sertraline in the 3-month extension study. Results showed that the total premenstrual scores from the Penn Daily Symptom Report (DSR) were lower in the half-cycle dosing group in each of the 3 treatment months but did not differ with statistical significance from the full-cycle dosing group. Further analysis of the 17 DSR items showed that mood swings, nervous tension, feeling out of control, and confusion were significantly lower (p < 0.05) at endpoint in the half-cycle dosing group. Overall, subjects who improved in prior treatment remained improved; approximately half the subjects who were unimproved at entry into the extension study improved, regardless of the dosing regimen. The results add support to other preliminary reports of efficacy of serotonergic antidepressants administered premenstrually and indicate the clinical importance of determining an optimal dose/benefit ratio of serotonergic antidepressants for PMS patients.

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 study's 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.

Depot medroxyprogesterone acetate or oral contraception in postpartum adolescents.

OBJECTIVE: To compare rates of method continuation and repeat pregnancy among postpartum adolescents selecting depot medroxyprogesterone acetate or oral contraceptives (OCs). METHODS: A retrospective study of 161 adolescents aged 19 years and younger who gave birth at an urban teaching hospital between May 1, 1994, and April 30, 1995, returned to the hospital's family planning clinic within 14 weeks of delivery and chose depot medroxyprogesterone acetate (n=111, 69%), or OC (n=50, 31%) as their postpartum contraceptive method. Most subjects were black (99%), single (97%), and on medical assistance (85%). Data were gathered 12-18 months postpartum (mean+/-standard deviation [SD] 14.5+/-1.6 months) by telephone interview and medical record review. The main outcome measures were method continuation and repeat pregnancy. RESULTS: The mean (+/-SD) age at delivery was 17.8+/-1.4 years. Variables differentiating subjects selecting depot medroxyprogesterone acetate or OC included multiparity (34% versus 12%, P < .05), mean age at first pregnancy (15.9 versus 16.6 years, P < .05), and mean age at first delivery (16.1 versus 16.9 years, P < .05). The survival curves for depot medroxyprogesterone acetate and OC continuation differed significantly (median duration of use 8.1 versus 5.4 months, respectively), but the continuation rates at 12 months were similar (34% versus 32%). The survival curves for repeat pregnancy among subjects selecting depot medroxyprogesterone acetate differed significantly from curves of those choosing OC, with repeat pregnancy rates of 15% and 36% by 15 months. Postpartum selection of OC was the only variable entering a Cox regression model designed to predict repeat pregnancy (relative risk 3.0, 95% confidence interval 1.4, 6.7). CONCLUSION: Adolescent mothers choosing depot medroxyprogesterone acetate or OC immediately postpartum face similarly high rates of method discontinuation and repeat pregnancy within 1 year.

Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria: a controlled study.

Gonadotropin-releasing hormone (GnRH) agonists have been shown to reduce symptoms of premenstrual syndrome (PMS). This randomized, placebo-controlled study examined the efficacy of the GnRH agonist, leuprolide acetate depot, in a clearly defined PMS sample versus women with premenstrual symptoms in combination with dysphoric symptoms throughout the cycle, termed the premenstrual exacerbation (PME) group. Evaluation included the Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and the subject Penn Dally Symptoms Report (DSR) maintained throughout the study. Thirty-three eligible women were randomized to double-blind treatment and administered 3.75 mg of depot leuprolide or a placebo once a month for 3 months. The subjects were seen for efficacy evaluations at the end of each cycle. Outcome measures were the DSRs and the 17-item Hamilton Depression Rating Scale (HAM-D17). The PMS leuprolide subjects improved significantly compared with the PMS placebo and PME leuprolide groups. The PME leuprolide group, who had dysphoric symptoms throughout the cycle, did not improve. Depression symptoms were at clinical levels premenstrually in the PMS and PME groups; following treatment they remitted in the PMS group but not in the PME leuprolide subjects. Efficacy did not occur until after several months of leuprolide treatment, but there was no evidence that PMS symptoms worsened with the onset of treatment. These results replicate the findings in our preliminary open-label study. Leuprolide reduced PMS symptoms to minimal levels where symptoms were limited to the luteal phase. Leuprolide was not effective for women with ongoing dysphoric symptoms, suggesting that premenstrual depression may have mechanisms different from those of other dysphoric mood disorders.

Sertraline versus desipramine in the treatment of premenstrual syndrome: an open-label trial.

BACKGROUND: Antidepressant medications have appeared to be effective treatments for premenstrual syndrome (PMS) in several small trials. This open-label study examined the efficacy of and tolerance for a new serotonergic antidepressant compared with a traditional tricyclic antidepressant in PMS treatment. METHOD: For two menstrual cycles in women meeting well-defined criteria for PMS, an open-label comparison of the serotonin selective sertraline (N = 17) and the noradrenergic desipramine (N = 15) was performed. Dose was flexible, with a mean dose in the second cycle of 87 mg/day for sertraline and 110 mg/day for desipramine. Outcome measures were the premenstrual daily symptom report (DSR) scores and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Sertraline and desipramine reduced depressive symptoms as assessed by the HAM-D, both achieving similar reductions in the HAM-D scores. Reduction of total premenstrual symptoms as assessed by the DSR score was observably greater with sertraline, but the difference compared with desipramine was not statistically significant in this small sample. Subjects were more likely to perceive desipramine side effects as intolerable; 4 of the 15 desipramine-treated subjects discontinued compared with none in the sertraline group. Subjects who were previously treated in a PMS program without good therapeutic response were less likely to respond to either medication, suggesting a treatment-resistant group. CONCLUSION: Sertraline and possibly desipramine appear to be effective treatments for PMS. Sertraline was better tolerated, resulting in greater patient acceptance. A placebo-controlled trial in which subjects are randomly assigned to the medication is clearly needed to support or refute these preliminary findings.

Fluvoxamine for premenstrual dysphoric disorder: a pilot study.

BACKGROUND: Serotonergic agents appear to be effective treatments for premenstrual symptoms in a number of small trials. The purpose of this open-label treatment study was to collect pilot information on the efficacy of fluvoxamine for premenstrual dysphoric disorder (PDD). METHOD: Twelve women who sought medical treatment for premenstrual symptoms were evaluated. The main outcome measure was the premenstrual score from daily symptom reports (DSRs) maintained by the subjects. After a 2-month screening period, 10 subjects who met DSM-IV criteria for PDD were treated with fluvoxamine taken daily for two menstrual cycles. The mean dose at 4 weeks was 85 mg/day; at 8 weeks, all subjects took 100 mg/day. RESULTS: The mean premenstrual DSR scores improved at 4 weeks from the pretreatment baseline (paired t test, p < .0008) and remained improved at 8 weeks at approximately the same level (p < .003). Symptoms with the greatest improvement (p < .003, significant with the Bonferroni adjustment) were irritability, anxiety, feeling out of control, and decreased interest in usual activity. Sixty percent (6/10) of the subjects reported at least a 50% reduction in the DSR scores, a conservative clinical definition of improvement. The mean premenstrual Hamilton Rating Scale for Depression scores decreased from 19 at the pretreatment baseline to 9 at the 4-week evaluation. The main side effects were insomnia (N = 6), fatigue (N = 4), dry mouth (N = 4), and nausea (N = 3) and were generally mild and transient. CONCLUSION: These promising pilot data show the importance of a controlled trial over a longer time period to provide definitive information on the efficacy of fluvoxamine for premenstrual dysphoric disorder.

A clinician's guide to the premenstrual syndrome.

Many women have menstrual symptoms, but relatively few have severe PMS. PMS is a well-defined premenstrual cluster of predominantly affective symptoms that disrupt a woman's daily functioning. PMS is diagnosed with prospective charting of symptoms and should be differentiated from nondisruptive menstrual symptoms, major affective disorders, and other common medical and gynecologic conditions. Most women with PMS can be helped. The serotonin reuptake inhibitors are becoming the first line of therapy for PMS because they are effective, easily tolerated, and free of major side effects. There is also evidence supporting the role of other antidepressants, anxiolytics, and GnRH agonists in the treatment of PMS. Although increasing control of one's life, promoting a healthy diet, the avoidance of salt and caffeine, vitamin supplementation, and exercise have not been proved as effective treatment for PMS, they should be promoted for their obvious general health benefits. No one treatment fits the heterogeneous PMS population. A trial of medication should be continued for two or three menstrual cycles with appropriate dose adjustments. If relief is not sufficient, other agents or other treatments should be initiated.

A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome.

OBJECTIVE: To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. DESIGN: Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. SETTING: University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. SUBJECTS: Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. INTERVENTION: A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. MAIN OUTCOME MEASURES: Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. RESULTS: Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. CONCLUSIONS: Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.

Emergency contraception.

Emergency contraception is the only form of contraception where implementation can occur after sexual relations or forced intercourse. Hormonal methods can be administered up to 72h after unprotected intercourse. Emergency contraception is safe, legal, and simple to administer. Widespread availability could dramatically decrease the number of unwanted pregnancies.

PIP: More widespread availability of emergency contraceptive methods has the potential to drastically reduce unwanted pregnancy. At present, only 3% of women use such methods and only 10% know how to obtain them; another 25-30% are unaware of this option. Use of the regimens is indicated in cases of rape, unprotected intercourse, and contraceptive mishaps such as condom breakage or skipping more than two oral contraceptive pills. Currently available regimens include 200 mcg of ethinyl estradiol and 2 mg of levonorgestrel taken in a split dose within 72 hours of unprotected intercourse, 0.75 mg of levonorgestrel taken within 8 hours of intercourse and repeated in 24 hours, 2-3 doses of 800 mg of the synthetic androgen danazol started within 72 hours of unprotected sex, insertion of a copper IUD, and a single dose of 600 mg of RU-486 within 72 hours; high doses of estrogen are no longer recommended due to serious side effects. Pregnancy rates range from 0.2-2.3% in users of combined estrogen and progesterone to 0.0-0.1% for the copper IUD and RU-486. The main side effects associated with these methods include nausea, vomiting, breast tenderness, and disruption of the menstrual cycle. Given the safety, simplicity, and effectiveness of these postcoital methods, it is recommended that all family planning programs make emergency contraception available.

Nefazodone in the treatment of premenstrual syndrome: a preliminary study.

Nefazodone, a new phenylpiperazine antidepressant agent with serotonin type 2 antagonism and serotonin reuptake inhibition, was evaluated in two patient groups to determine its effectiveness in reducing the symptoms of premenstrual syndrome (PMS). The two studied groups were PMS patients with no coexisting major depression or dysthymia (N = 23) and PMS patients with current major depression or dysthymia, termed the premenstrual exacerbation group (N = 24). The two patient groups received open-label nefazodone for 8 weeks, with optional maintenance at the same dose for up to 1 year. The initial dose was 100 mg, titrated to 600 mg/day, on a twice-daily dosing schedule. Symptoms were assessed by the Hamilton Rating Scale for Depression and by Daily Symptom Ratings. Premenstrual symptoms improved significantly from pretreatment baseline values, with similar improvement for the PMS and premenstrual exacerbation groups. Significantly improvement occurred by the end of the first treated cycle (4 weeks of therapy), at an average dose of 245 (range, 100 to 400) mg, and was maintained thereafter. Nefazodone was well tolerated, side effects were often transient, and the most common were nausea and headache. Forty-seven of 54 patients completed 2 months of therapy, with a mean daily nefazodone dose of 319 mg at the 2-month point. A placebo-controlled study should be conducted to confirm and extend these promising preliminary findings.

Contraception choice and sexually transmitted disease.

Sexually active couples need to be concerned with the risk of sexually transmitted diseases (STDs) and how their choice of contraception influences that risk. Condoms provide the best documented protection against such pathogens as: gonorrhea, herpes simplex virus (HSV), hepatitis B, HIV, and chlamydia. Female dependent barrier methods also provide protection against most STDs and also possibly HIV. Most hormonal non-barrier contraceptives, although providing excellent protection against unwanted pregnancies, provide little protection against STDs. Oral contraceptive pills (OCP) may increase the risk of infection with human papillomavirus (HPV) and cervical infections of chlamydia. Individuals at high risk for both an unwanted pregnancy and an STD should be counseled to use both a hormonal and barrier contraceptive. Recently, nonoxynol-9 (N-9) and OCP use have been associated with an increase in HIV infection in African women at high risk for HIV. This association has not been found in other studies and currently does not outweigh the proven benefits of these contraceptive methods.