Ellen Wells

Menopausal symptoms and treatment-related effects of estrogen and progestin in the women's health initiative

OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50–79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40–5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04–3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90–3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24–1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08–1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59–5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44–5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27–1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08–1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery. LEVEL OF EVIDENCE: I

Urinary incontinence in pregnancy and the puerperium: A prospective study

OBJECTIVE Pregnancy and childbirth are commonly thought to be associated with the development of urinary incontinence and lower urinary tract symptoms. The purpose of this study was to assess the relationship, if any, between pregnancy and the development of lower urinary tract symptoms. STUDY DESIGN A prospective study of lower urinary tract symptoms was carried out in a cohort of pregnant women who answered a series of symptom questionnaires and kept a 24-hour bladder chart on which frequency of urination and volumes voided were recorded throughout pregnancy and for 8 weeks after birth. RESULTS A total of 123 women participated in the study. Mean daily urine output (P =.01) and the mean number of voids per day (P =.01) increased with gestational age and declined after delivery. Episodes of urinary incontinence peaked in the third trimester and improved after birth (P =.001). White women had higher mean voided volumes and fewer voiding episodes than did black women. Ingestion of caffeine was associated with smaller voided volumes and greater frequency of urination. CONCLUSION Pregnancy is associated with an increase in urinary incontinence. This phenomenon decreases in the puerperium. Pregnancy and childbirth trauma are important factors in the development of urinary incontinence among women. These findings warrant further investigation.

Transdermal versus oral estrogen therapy in postmenopausal smokers: Hemodynamic and endothelial effects

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular β2-adrenoceptor responsivity. METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and β-adrenoceptor responsivity. RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular β2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to premenopausal values in the group receiving transdermal estrogen compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease. LEVEL OF EVIDENCE: I

Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial.

Background Non-surgical treatment for stress urinary incontinence (SUI) is recommended as first-line therapy, yet few prospective studies and no randomized trials compare the most common non-surgical treatments for SUI. Purpose To present the design and methodology of the ambulatory treatments for leakage associated with stress (ATLAS) trial, a randomized clinical trial comparing three interventions for predominant SUI in women: intravaginal continence pessary; behavioral therapy (including pelvic floor muscle training and exercise and bladder control strategies); and a combination of the two treatments. Methods Treatment outcome measures, collected at 12 weeks and six and 12 months post randomization, include the Patient Global Impression of Improvement (PGI-I), the Stress Incontinence Scale of the Pelvic Floor Distress Inventory (PFDI), seven-day bladder diaries, Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12), Patient Satisfaction Questionnaire (PSQ) and the Medical Outcomes Study Short Form Health Survey (SF-36). Limitations The study design reduces most common biases, but some degree of selection bias may remain. Conclusion This trial will provide useful information to help counsel women with stress and mixed incontinence about the relative efficacy and satisfaction with pessary, behavioral therapy and both treatments combined.

Smoking, oral contraceptives, and cardiovascular reactivity to stress

Objective To investigate the effects of smoking and oral contraceptive (OC) formulation on hemodynamic responses to stress in women. Methods Twenty-three smokers and 23 nonsmokers taking different OC formulations (ie, containing higher or lower androgenic progesterones) were tested for cardiovascular reactivity during mathematic, speech preparation, speech, and cold pressor stress. Results During mental stress, smokers, regardless of OC formulation, had lower systolic blood pressure (BP) (eg, 10.2 versus 15.1 mmHg, P < .05), heart rate (eg, 7.5 versus 15.0 beats per minute, P < .01), and cardiac index reactivity (eg, 0.08 versus 0.48 L/minute/M2, P < .01) but greater vascular resistance index responses (eg, 115.6 versus −51.9 dyne-sec • cm−5 • M2, P < .05). Women who took higher androgen OCs, regardless of smoking status, showed greater vascular resistance index increases during speech stress than those who took lower androgen OCs (215.8 versus 9.4 dyne-sec • cm−5 • M2, P < .05). Smokers who took more androgenic OCs had greater systolic BP responses to speech preparation compared with nonsmokers who took the same OCs (12.1 versus 6.1 mmHg, P < .05), and smokers who took lower androgen OCs (12.1 versus 4.4 mmHg, P < .05). Least-squares means examination found that smokers who took higher androgen OCs had greater vascular resistance index increases to all mental stressors than nonsmokers who took lower androgen OCs. Conclusion Higher androgen OCs might be linked to greater vascular and BP increases during stress, especially in smokers. Given that increased vascular resistance and BP contribute to cardiovascular mortality, those results suggest that androgenic profiles of synthetic progesterones might be an important consideration in OC choice.

Cervical dilation: A comparison of Lamicel and Dilapan

A randomized prospective double-blind study compares the dilatation achieved with Lamicel and Dilapan synthetic dilators in the setting of second-trimester elective abortions. A total of 51 patients with estimated gestational ages of 13 to 16 weeks had either Lamicel dilators or Dilapan dilators placed approximately 20 hours before dilation and evacuation. The placement and removal were by someone other than the operator. The operator then recorded the number of the Pratt dilator at which resistance was first met. The mean for the Lamicel group was French size 38.5 +/- 6.4. The mean for the Dilapan group was French size 50.4 +/- 9.6. In the Dilapan group there were six patients for whom cervical resistance was never reached. The results indicate a significantly greater dilatation was achieved with Dilapan dilators. This correlation was also noted within the subsets of nulliparous and parous patients.

Assessment of pelvic floor function: A series of simple tests in nulliparous women

The aim of the study was to assess normal ranges, variations, test-retest reliability and correlations between tests for a battery of simple, minimally invasive tests of pelvic floor function in nulliparous asymptomatic women. Women were recruited by advertisement and underwent dipstick urinalysis, simple cystometrics, provocative tests for incontinence, Q-tip test and surface electromyography with acrylic plug electrodes. Subjects were retested at a later date. Nineteen subjects underwent initial testing and 12 were retested. A wide range of normal values was obtained. Cystometric measures of first and strong urge to void the maximum bladder capacity, Q-tip test and rectal perineometry had significant correlations between the two visits. There were no significant between-test correlation coefficients. It was concluded that the simple tests used demonstrate a mixed ability to follow pelvic floor function longitudinally.

Effect of anticholinergic use for the treatment of overactive bladder on cognitive function in postmenopausal women.

BACKGROUND Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs, including cognitive changes. OBJECTIVE The objective of this study was to investigate the effect of an anticholinergic medication, trospium chloride, on cognitive function in postmenopausal women being treated for OAB. METHODS This was a prospective cohort study conducted at a urogynaecology clinic at one academic medical centre from January to December 2010, with 12-week follow-up after medication initiation. Women aged 55 years or older seeking treatment for OAB and opting for anticholinergic therapy were recruited. Baseline cognitive function was assessed via the Hopkins Verbal Learning Test-Revised Form (HVLT-R) [and its five subscales], the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality-of-life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance. The main outcome measure was change in HVLT-R score at Week 4 after medication initiation, compared with baseline (pre-medication) score. RESULTS Of 50 women enrolled, 35 completed the assessment. The average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p = 0.037), HVLT-R Delayed Recognition subscale (p = 0.011) and HVLT-R Recognition Bias subscale (p = 0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p = 0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p < 0.05). CONCLUSION Cognitive function exhibited early changes after initiation of trospium chloride but normalized within 4 weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.

The effect of dehydroepiandrosterone (DHEA) on recognition memory decision processes and discrimination in postmenopausal women

In this article, the theoretical distinction between recognition memory decision and discrimination processes is used to explore the effect of dehydroepiandrosterone (DHEA) in postmenopausal women. DHEA is an adrenal steroid that diminishes with aging. It has enhanced memory in laboratory animals. An 8-week placebo-controlled, double-blind experiment in which 30 women (ages 39–70) received a 50-mg/day oral dose of DHEA for 4 weeks demonstrated that DHEA made subjects more conservative (i.e., less likely to call test items “old”) in their recognition memory decisions and enhanced recognition memory discrimination for items presented briefly. The former result may reflect an empirical regularity (Hirshman, 1995) in whichrecent strong memory experiences make participants more conservative. The latter result may reflect the effect of DHEA on visual perception, with consequent effects on memory. These results suggest the methodological importance of focusing on decision processes when examining the effects of hormones on memory.

Changes in physical activity after abdominal sacrocolpopexy for advanced pelvic organ prolapse

OBJECTIVE The objective of the study was to describe changes in physical activity 1 year after sacrocolpopexy for pelvic organ prolapse. STUDY DESIGN This was a prospective cohort of 301 randomized trial participants. RESULTS Compared with baseline, 1 year after surgery, 36% increased, 18% decreased, and 47% did not change preoperative exercise intensity level. In contrast, women were more likely to reduce (24%) than increase (11%) the frequency of major effort activities, like heavy lifting. Of 99 women who reported preoperatively that prolapse interfered substantially with doing exercise or recreation, house/yard work, or work outside the home, 83 (84%) reported no substantial interference 1 year later. After surgery, women reporting substantial interference from prolapse or treatment had similar rates of interval treatment for stress incontinence or prolapse as women not reporting substantial interference. CONCLUSION After sacrocolpopexy, one third of women increased exercise intensity, few increased major effort activities, and most reported that prolapse no longer interfered with activities.