Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 µg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing.

Differences in menopausal symptoms and female sexual function by region and ethnicity in West Texas and Central Arizona: a cross-sectional survey.

OBJECTIVE: To evaluate menopausal symptoms and sexual problems in Hispanic and non-Hispanic women in two Southwest areas. METHODS: An anonymous survey including the Green Climacteric Scale (GCS), Female Sexual Function Index (FSFI), and demographics was distributed to English and Spanish-speaking women age 40 to 60 in Scottsdale, Arizona, and West Texas. FSFI for sexually active women and GCS scores for the Hispanic and non-Hispanic women in Texas were analyzed with multivariable analysis and compared between Texas and Arizona for Non-Hispanic participants. RESULTS: Predominantly non-Hispanic women (70%), average age 51.5 (SD = 7.25) completed questionnaires (199 West Texas, 163 Scottsdale). A majority of sexually active women (88%) were found to be at risk of sexual dysfunction. Within the Texas cohort, GCS score was estimated to be 3.49 points lower (less symptoms) in Hispanic versus non-Hispanic participants [95% CI -6.58 to -0.40, P = 0.03], and FSFI score was estimated to be 2.31 points lower (more symptoms) in Hispanic versus non-Hispanic participants [95% CI -4.49 to -0.14, P = 0.04]. Among non-Hispanic women, GCS scores were lower (less symptoms) in Texas versus Arizona by 10.25 points [95% CI -14.83 to -5.66, P < 0.01], while FSFI scores were higher overall (less symptoms) in Texas by 3.65 points [95% CI 0.53-6.77), P = 0.02]. All FSFI and GCS scores were adjusted for multiple variables. CONCLUSIONS: In a group of menopausal women from the Southwest, most reported symptoms were consistent with FSD, and the degree of sexual problems appeared to be greater in the Hispanic participants from Texas.

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Mifepristone versus laminaria: a randomized controlled trial of cervical ripening in midtrimester termination.

BACKGROUND: Mifepristone was compared with laminaria for cervical ripening in second-trimester induction of labor (IOL). STUDY DESIGN: We performed a randomized, controlled, open-label study of women undergoing second-trimester IOL for fetal demise, aneuploidy or anomalies at a single tertiary care center from January 2004 to May 2006. Main outcome measures were induction-to-delivery time and pain with cervical ripening. RESULTS: Of 50 eligible women, 37 were enrolled in the study, of whom 33 completed the study: 16 were randomized to laminaria and 17 to mifepristone. Induction-to-delivery time was significantly shorter in the mifepristone arm (mean=10 h vs. 16 h, p=.01; median=7.5 h vs. 13.4 h, p=.01). Pain with cervical ripening was also significantly less in the mifepristone group than in the laminaria group (median=1 vs. 6 on an 11-point visual analogue scale, p<.001). Maternal age, parity, gestational age, fetal demise prior to induction, need for postpartum curettage, blood loss, pain during induction, delivery and at the time of discharge were not significantly different between the two groups. CONCLUSION: Mifepristone shortens the induction-to-delivery time and decreases pain with cervical ripening when compared with laminaria for second-trimester induction.

Symptoms of depressed mood, disturbed sleep, and sexual problems in midlife women: cross-sectional data from the Study of Women's Health Across the Nation.

BACKGROUND: Women report many nonvasomotor symptoms across the menopausal transition, including sleep disturbances, depressed mood, and sexual problems. The co-occurrence of these three symptoms may represent a specific menopausal symptom triad. We sought to evaluate the interrelatedness of disturbed sleep, depressed mood, and sexual problems in the Study of Women's Health Across the Nation (SWAN) and determine the characteristics of women exhibiting this symptom triad. METHODS: SWAN is a multisite, multiethnic observational cohort study of the menopausal transition in the United States. Sleep disturbance, sexual problems, and depressed mood were determined based on self-report. Women who reported all three symptoms simultaneously were compared to those who did not. Logistic regression models estimated the association of demographic, psychosocial, and clinical characteristics with the symptom triad. RESULTS: Study participants (n=1716) were 49.8 years old on average and primarily in very good or excellent health. Sixteen and a half percent had depressed mood, 36.6% had a sleep problem, and 42.2% had any sexual problem. Five percent of women (n=90) experienced all three symptoms. Women with the symptom triad compared with those without had lower household incomes, less education, were surgically postmenopausal or late perimenopausal, rated their general health as fair or poor, and had more stressful life events and lower social support. CONCLUSIONS: The symptom triad of sleep disturbance, depressed mood, and sexual problems occurred in only 5% of women, and occurred most often among women with lower socioeconomic status, greater psychosocial distress, and who were surgically menopausal or in the late perimenopause.

Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: a novel heuristic model.

OBJECTIVE: In this conceptual review, the authors propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition ("perimenopausal depression") involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation. METHOD: The relevant literature in perimenopausal depression, including prevalence, predictors, and treatment with estrogen therapy, was reviewed. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development. RESULTS: The rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and derived neurosteroids result in alterations in regulation of the HPA axis by γ-aminobutyric acid (GABA). The authors' heuristic model suggests that for some women, failure of the GABAA receptor to regulate overall GABA-ergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress and generating greater vulnerability to depression. CONCLUSIONS: The proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of midlife to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders, such as postpartum depression and premenstrual dysphoric disorder.

Trends in gestational choriocarcinoma: a 27-year perspective.

OBJECTIVE: To evaluate trends in incidence and survival rates for gestational choriocarcinoma with the use of population-based data. METHODS: Overall and 5-year average age-adjusted incidence rates were computed with the Surveillance, Epidemiology, and End Results program public-use database. Differences by age at diagnosis, race, stage, registry, and over calendar time were compared by Poisson regression, and survival censored for deaths other than choriocarcinoma by log-rank tests and Cox's proportional hazard ratios. RESULTS: Between 1973 and 1999, 450 cases were recorded. The annualized age-adjusted incidence rate for choriocarcinoma was 0.133 per 100,000 woman-years and decreased by 49.7% (2.8% per year). By race (whites, blacks, and others), incidence rates declined by 62.3%, 27.2%, and 54.3%, respectively. In the Poisson model evaluating incidence rates, age, race, registry, and stage were significant main effects. Compared with whites, the relative risk was higher for blacks (2.14, 95% confidence interval [CI] 1.60, 2.86) and others (2.30, 95% CI 1.67, 3.18). Rates were highest in Utah and lowest in Iowa. By age at diagnosis, rates were higher in 20-39-year-olds. The 5-year relative survival rate was 89.5%. Censored survival was significantly lower among blacks (whites 92.4%, blacks 84.9%, others 87.1%, P = .045), for advanced disease (localized 94.5%, regional 92.9%, distant 87.1%, P = .02), and with increasing age at diagnosis (P = .017). Age and calendar time significantly influenced censored survival independent of stage and registry. CONCLUSION: Gestational choriocarcinoma incidence rates have declined and survivals have improved, but blacks continue to have higher incidence and lower survival rates.

What midlife women want from gynecologists: a survey of patients in specialty and private practices.

BACKGROUND: This study characterized the self-reported reason for a gynecology visit among midlife women in three different practice settings. We hypothesized that women seeking specialty care were more likely to report nonvasomotor symptoms potentially related to the menopausal transition. METHODS: Participants were 625 women aged 40-60 seen by gynecologists at three sites: an urban, academic, gynecologic menopause practice (Midlife Practice, or MLP) and urban (site A) and suburban (site B) locations of a general, nonacademic obstetrics and gynecology practice. Participants completed a self-report questionnaire asking them to choose and weigh the reason for their visit as "very much," "somewhat," or "not at all" for 15 common gynecologic and menopausal concerns. Demographic questions included age, self-rated health status, race/ethnicity, difficulty of paying for basics, and education. Comparisons between the three groups were made using parametric and nonparametric tests as appropriate. The main outcome measure was the response to the reason for participants' visit compared across the three sites. RESULTS: Women presenting to the MLP were significantly older and more likely to report vasomotor symptoms (VMS), moodiness, sexual problems, sleep problems, and weight and to learn more about menopause. When "very much" and "somewhat" reasons were combined, nearly 80% of the MLP responses listed sleep problems, 60% listed vaginal dryness or low desire, 34% listed weight gain, and 30.7% listed mood. CONCLUSIONS: Midlife women seeking care in a menopause gynecology practice had significantly more visits for vasomotor and nonvasomotor concerns than did women seeing general gynecologists. Women sought care for a broad range of concerns that are not typically in gynecologists' scope of practice, including sleep disturbances, moodiness, and weight management.

Postpartum lipid levels in women with major depression.

BACKGROUND: Maternal plasma lipids, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), increase during pregnancy, remaining elevated over prepregnancy levels through the immediate postpartum period. Triglycerides decrease rapidly to prepregnancy levels after delivery. Few data on postpartum lipid levels are available, and levels in postpartum women with depression have not been evaluated. We sought to determine the cross-sectional levels of total cholesterol, LDL-C, HDL-C, and triglycerides between 1 and 14 weeks postpartum in postpartum women with DSM-4 diagnoses of major depression and determine if they are similarly elevated to published levels in other postpartum populations. METHODS: As part of screening for a randomized controlled trial comparing treatments for postpartum depression (PPD), women (n=120) had postpartum fasting lipid levels determined. Linear regression models were used to assess the association between time postpartum and lipid levels. Analysis of covariance models (ANCOVA) assessed the association of baseline characteristics with lipids. RESULTS: Total cholesterol levels were >200 mg/dL in 45% of the sample at baseline. Mean baseline total cholesterol was 196±39 mg/dL. There was an inverse linear relationship between postpartum week and total cholesterol, with cholesterol values decreasing an average of 4.5 mg/dL per week. Similarly, LDL-C and HDL-C trended down over time. Triglycerides were stable and within the normal range during the observation period. CONCLUSIONS: Total cholesterol, HDL-C, and LDL-C are significantly elevated in the early postpartum period and do not return to <200 mg/dL until 6 weeks postpartum in women with PPD. The magnitude and duration of elevation are consistent with the sparse published data on nondepressed women.

Disturbed sleep, a novel risk factor for preterm birth?

OBJECTIVE: The etiology of preterm birth (PTB) is likely caused by multiple factors, which may include disturbed sleep. We evaluated whether sleep disturbance was associated with PTB and whether the association was affected by other psychosocial risk factors. METHODS: Pregnant women (n=217) for whom we had depression and sleep data at 20 or 30 weeks gestation and delivery information were evaluated. Logistic models were used to test the hypotheses that disturbed sleep was associated with PTB. RESULTS: Time in bed at 20 weeks was significantly associated with risk for preterm delivery (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.08-1.88). However, after controlling for depression/selective serotonin reuptake inhibitors (SSRI) status, history of PTB, age, employment, and marital status, this relationship was no longer significant (OR 1.26, 95% CI .92-1.71). No other relationships were significant. CONCLUSIONS: We report preliminary evidence suggesting that poor sleep may contribute to risk for PTB. Although it is speculative and additional work is needed to confirm or refute whether sleep is an independent or mediating risk factor for PTB, disturbed sleep does appear to play a role in adverse pregnancy outcomes.

Bone resorption and fracture across the menopausal transition: the Study of Women's Health Across the Nation.

OBJECTIVE: Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women. METHODS: Women attended up to nine clinic visits for an average of 7.6 ± 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs. RESULTS: Women who experienced fractures (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured premenopausally was associated with a higher fracture risk during menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46; 95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61-6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08-2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD. CONCLUSIONS: A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength.

A higher sense of purpose in life is associated with sexual enjoyment in midlife women.

OBJECTIVE: The aim of this study was to understand the association between sense of purpose in life and sexual well-being in a cohort of midlife women. METHODS: Participation in partnered sexual activities and indicators of sexual well-being (the engagement in and enjoyment of sexually intimate activities) were measured in a longitudinal cohort of 677 eligible women aged 40 to 65 years. At a single time point, women completed the Life Engagement Test, a measure of life purpose. Univariable and multivariable mixed models were used to assess the association between the Life Engagement Test and longitudinal sexual well-being. RESULTS: A higher sense of purpose in life was associated with higher levels of enjoyment (coefficient = 2.89, P < 0.001) but not with participation in partnered sexual activity (coefficient = 0.49, P = 0.63) or engagement in partnered sexually intimate activities (coefficient = 1.0, P = 0.30). Participation was associated with younger age, lower body mass index, being married, reporting any vaginal dryness, and better emotional well-being. Hormone therapy use approached, but did not reach significance in association with participation, with P = 0.05. Engagement in sexually intimate activities was associated with younger age, more social support, and better emotional well-being. Higher levels of enjoyment were associated with more social support, better emotional well-being, and less vaginal dryness. Menopause status was not associated with engagement or enjoyment, and only being 5 years or more postmenopausal was related to decreased participation. CONCLUSIONS: Higher sense of purpose in life is associated with more enjoyment of sexually intimate activities, adjusting for other known factors that influence sexual well-being and independent of demographic factors and menopause or hormone therapy status.