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American Family Physician Dec 2016The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone... (Review)
Review
The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.
Topics: Acupuncture Therapy; Administration, Intravaginal; Amines; Antidepressive Agents; Atrophy; Cyclohexanecarboxylic Acids; Dietary Supplements; Drug Therapy, Combination; Dyspareunia; Estrogen Replacement Therapy; Estrogens; Exercise Therapy; Female; Gabapentin; Hot Flashes; Humans; Hypnosis; Indoles; Menopause; Paroxetine; Progestins; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vasomotor System; Venlafaxine Hydrochloride; gamma-Aminobutyric Acid
PubMed: 27929271
DOI: No ID Found -
The Cochrane Database of Systematic... Aug 2016Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring). This is an update of a Chochrane systematic review; the original version was first published in October 2006.
OBJECTIVES
The objective of this review was to compare the efficacy and safety of intra-vaginal oestrogenic preparations in relieving the symptoms of vaginal atrophy in postmenopausal women.
SEARCH METHODS
We searched the following databases and trials registers to April 2016: Cochrane Gynaecology and Fertility Group Register of trials, The Cochrane Central Register of Controlled Trials (CENTRAL; 2016 issue 4), MEDLINE, Embase, PsycINFO, DARE, the Web of Knowledge, OpenGrey, LILACS, PubMed and reference lists of articles. We also contacted experts and researchers in the field.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for at least 12 weeks for the treatment of symptoms resulting from vaginal atrophy or vaginitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were improvement in symptoms (participant-assessed), and the adverse event endometrial thickness. Secondary outcomes were improvement in symptoms (clinician-assessed), other adverse events (breast disorders e.g. breast pain, enlargement or engorgement, total adverse events, excluding breast disorders) and adherence to treatment. We combined data to calculate pooled risk ratios (RRs) (dichotomous outcomes) and mean differences (MDs) (continuous outcomes) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
MAIN RESULTS
We included 30 RCTs (6235 women) comparing different intra-vaginal oestrogenic preparations with each other and with placebo. The evidence was low to moderate quality; limitations were poor reporting of study methods and serious imprecision (effect estimates with wide confidence intervals)1. Oestrogen ring versus other regimensOther regimens included oestrogen cream, oestrogen tablets and placebo. There was no evidence of a difference in improvement in symptoms (participant assessment) either between oestrogen ring and oestrogen cream (odds ratio (OR) 1.33, 95% CI 0.80 to 2.19, two RCTs, n = 341, I(2) = 0%, low-quality evidence) or between oestrogen ring and oestrogen tablets (OR 0.78, 95% CI 0.53 to 1.15, three RCTs, n = 567, I(2) = 0%, low-quality evidence). However, a higher proportion of women reported improvement in symptoms following treatment with oestrogen ring compared with placebo (OR 12.67, 95% CI 3.23 to 49.66, one RCT, n = 67). With respect to endometrial thickness, a higher proportion of women who received oestrogen cream showed evidence of increase in endometrial thickness compared to those who were treated with oestrogen ring (OR 0.36, 95% CI 0.14 to 0.94, two RCTs, n = 273; I(2) = 0%, low-quality evidence). This may have been due to the higher doses of cream used. 2. Oestrogen tablets versus other regimensOther regimens in this comparison included oestrogen cream, and placebo. There was no evidence of a difference in the proportions of women who reported improvement in symptoms between oestrogen tablets and oestrogen cream (OR 1.06, 95% CI 0.55 to 2.01, two RCTs, n = 208, I(2) = 0% low-quality evidence). A higher proportion of women who were treated with oestrogen tablets reported improvement in symptoms compared to those who received placebo using a fixed-effect model (OR 12.47, 95% CI 9.81 to 15.84, two RCTs, n = 1638, I(2) = 83%, low-quality evidence); however, using a random-effect model did not demonstrate any evidence of a difference in the proportions of women who reported improvement between the two treatment groups (OR 5.80, 95% CI 0.88 to 38.29). There was no evidence of a difference in the proportions of women with increase in endometrial thickness between oestrogen tablets and oestrogen cream (OR 0.31, 95% CI 0.06 to 1.60, two RCTs, n = 151, I(2) = 0%, low-quality evidence).3. Oestrogen cream versus other regimensOther regimens identified in this comparison included isoflavone gel and placebo. There was no evidence of a difference in the proportions of women with improvement in symptoms between oestrogen cream and isoflavone gel (OR 2.08, 95% CI 0.08 to 53.76, one RCT, n = 50, low-quality evidence). However, there was evidence of a difference in the proportions of women with improvement in symptoms between oestrogen cream and placebo with more women who received oestrogen cream reporting improvement in symptoms compared to those who were treated with placebo (OR 4.10, 95% CI 1.88 to 8.93, two RCTs, n = 198, I(2) = 50%, low-quality evidence). None of the included studies in this comparison reported data on endometrial thickness.
AUTHORS' CONCLUSIONS
There was no evidence of a difference in efficacy between the various intravaginal oestrogenic preparations when compared with each other. However, there was low-quality evidence that intra-vaginal oestrogenic preparations improve the symptoms of vaginal atrophy in postmenopausal women when compared to placebo. There was low-quality evidence that oestrogen cream may be associated with an increase in endometrial thickness compared to oestrogen ring; this may have been due to the higher doses of cream used. However there was no evidence of a difference in the overall body of evidence in adverse events between the various oestrogenic preparations compared with each other or with placebo.
Topics: Administration, Intravaginal; Aged; Atrophy; Estradiol; Estrogens; Female; Humans; Hydrogen-Ion Concentration; Isoflavones; Middle Aged; Postmenopause; Randomized Controlled Trials as Topic; Tablets; Vagina; Vaginal Creams, Foams, and Jellies; Vaginitis
PubMed: 27577677
DOI: 10.1002/14651858.CD001500.pub3 -
Women's Midlife Health 2015Female sexual dysfunction occurs frequently in midlife breast cancer survivors (BCS) and encompasses problems with sexual desire, interest, arousal, orgasm and... (Review)
Review
Female sexual dysfunction occurs frequently in midlife breast cancer survivors (BCS) and encompasses problems with sexual desire, interest, arousal, orgasm and genitopelvic pain. Although common, sexual problems are under-diagnosed and under-treated in BCS. The objective of this review was to assess primary studies that intervene on sexual dysfunction in BCS. In February 2015, PubMed, SCOPUS, CINAHL, COCHRANE and Web of Science databases were systematically searched for randomized controlled clinical trials (RCTs) of vaginal (lubricants, moisturizers, estrogens, dehydroepiandrosterone [DHEA], testosterone, vibrators, dilators), systemic (androgens, anti-depressants, flibanserin, ospemifene), physical therapy (physical activity, pelvic floor training), counseling and educational interventions on sexual function in BCS. Observational studies of vaginal interventions were also included due to the paucity of RCTs. The search yielded 1414 studies, 34 of which met inclusion criteria. Both interventions and outcomes, measured by 31 different sexual function scales, were heterogeneous, and therefore data were not pooled. The review found that regular and prolonged use of vaginal moisturizers was effective in improving vaginal dryness, dyspareunia, and sexual satisfaction. Educational and counseling interventions targeting sexual dysfunction showed consistent improvement in various aspects of sexual health. No consistent improvements in sexual health were observed with physical activity, transdermal testosterone or hot flash interventions. There was a lack of BCS-specific data on vaginal lubricants, vibrators, dilators, pelvic floor therapy, flibanserin or ospemifene. Overall, the quality of evidence for these studies was moderate to very low. Because each of the interventions with BCS data had limited efficacy, clinical trials to test novel interventions are needed to provide evidence-based clinical recommendations and improve sexual function in BCS.
PubMed: 30766696
DOI: 10.1186/s40695-015-0009-4 -
The Cochrane Database of Systematic... Apr 2015Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective.
OBJECTIVES
To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism.
DATA COLLECTION AND ANALYSIS
Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses.
MAIN RESULTS
We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs.
AUTHORS' CONCLUSIONS
Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.
Topics: 5-alpha Reductase Inhibitors; Adult; Androgen Antagonists; Body Mass Index; Contraceptive Agents, Female; Cyproterone Acetate; Desogestrel; Drug Combinations; Eflornithine; Ethinyl Estradiol; Female; Finasteride; Flutamide; Hirsutism; Humans; Hypoglycemic Agents; Metformin; Quality of Life; Randomized Controlled Trials as Topic; Spironolactone
PubMed: 25918921
DOI: 10.1002/14651858.CD010334.pub2 -
The Cochrane Database of Systematic... Jan 2015During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of various perimenopausal and postmenopausal symptoms (for example hot flushes, night sweats, vaginal dryness). Dehydroepiandrosterone (DHEA) is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens. It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function (for example libido, dyspareunia, satisfaction). Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety. This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials.
OBJECTIVES
To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase.
SEARCH METHODS
The databases that we searched (3 June 2014) with no language restrictions applied were the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the trials registers. Reference lists of retrieved articles were checked.
SELECTION CRITERIA
We included randomised controlled trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment for a minimal treatment duration of seven days in peri- and postmenopausal women.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data after assessing eligibility for inclusion and quality of studies. Authors were contacted for additional information.
MAIN RESULTS
Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo.There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison.There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%).
AUTHORS' CONCLUSIONS
There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo.
Topics: Acne Vulgaris; Dehydroepiandrosterone; Dyspareunia; Estrogens; Female; Hot Flashes; Humans; Perimenopause; Postmenopause; Quality of Life; Randomized Controlled Trials as Topic; Selection Bias; Sweating
PubMed: 25879093
DOI: 10.1002/14651858.CD011066.pub2 -
Obstetrics and Gynecology Dec 2014To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide... (Review)
Review
OBJECTIVE
To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines.
DATA SOURCES
MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.
METHODS OF STUDY SELECTION
We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence.
TABULATION, INTEGRATION, AND RESULTS
Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.
CONCLUSION
All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia.
CLINICAL TRIAL REGISTRATION
PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42013006656.
Topics: Administration, Intravaginal; Atrophic Vaginitis; Estrogens; Female; Humans; Menopause; Urologic Diseases
PubMed: 25415166
DOI: 10.1097/AOG.0000000000000526 -
The Cochrane Database of Systematic... Apr 2013The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance.
OBJECTIVES
To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs).
SEARCH METHODS
Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials.
SELECTION CRITERIA
We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC.
DATA COLLECTION AND ANALYSIS
Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review.
MAIN RESULTS
We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group.
AUTHORS' CONCLUSIONS
Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.
Topics: Consumer Behavior; Contraceptive Agents, Female; Contraceptive Devices, Female; Contraceptives, Oral, Combined; Drug Implants; Female; Humans; Medication Adherence; Menstrual Cycle; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 23633314
DOI: 10.1002/14651858.CD003552.pub4 -
The Cochrane Database of Systematic... Sep 2012Menopause can be a distressing and disruptive time for many women, with many experiencing hot flushes, night sweats, vaginal atrophy and dryness. Postmenopausal women... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Menopause can be a distressing and disruptive time for many women, with many experiencing hot flushes, night sweats, vaginal atrophy and dryness. Postmenopausal women are also at increased risk of osteoporosis. Interventions that decrease the severity and frequency of these menopausal symptoms are likely to improve a woman's well-being and quality of life. Hormone therapy has been shown to be effective in controlling the symptoms of menopause; however, many potentially serious adverse effects have been associated with this treatment. Evidence from experimental studies suggests that black cohosh may be a biologically plausible alternative treatment for menopause; even so, findings from studies investigating the clinical effectiveness of black cohosh have, to date, been inconsistent.
OBJECTIVES
To evaluate the clinical effectiveness and safety of black cohosh (Cimicifuga racemosa or Actaea racemosa) for treating menopausal symptoms in perimenopausal and postmenopausal women.
SEARCH METHODS
Relevant studies were identified through AARP Ageline, AMED, AMI, BioMed Central gateway, CAM on PubMed, CINAHL, CENTRAL, EMBASE, Health Source Nursing/Academic edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines comprehensive database, PsycINFO, TRIP database, clinical trial registers and the reference lists of included trials; up to March 2012. Content experts and manufacturers of black cohosh extracts were also contacted.
SELECTION CRITERIA
All randomised controlled trials comparing orally administered monopreparations of black cohosh to placebo or active medication in perimenopausal and postmenopausal women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data and completed the 'Risk of bias' assessment. Study authors were contacted for missing information.
MAIN RESULTS
Sixteen randomised controlled trials, recruiting a total of 2027 perimenopausal or postmenopausal women, were identified. All studies used oral monopreparations of black cohosh at a median daily dose of 40 mg, for a mean duration of 23 weeks. Comparator interventions included placebo, hormone therapy, red clover and fluoxetine. Reported outcomes included vasomotor symptoms, vulvovaginal symptoms, menopausal symptom scores and adverse effects. There was no significant difference between black cohosh and placebo in the frequency of hot flushes (mean difference (MD) 0.07 flushes per day; 95% confidence interval (CI) -0.43 to 0.56 flushes per day; P=0.79; 393 women; three trials; moderate heterogeneity: I(2) = 47%) or in menopausal symptom scores (standardised mean difference (SMD) -0.10; 95% CI -0.32 to 0.11; P = 0.34; 357 women; four trials; low heterogeneity: I(2) = 21%). Compared to black cohosh, hormone therapy significantly reduced daily hot flush frequency (three trials; data not pooled) and menopausal symptom scores (SMD 0.32; 95% CI 0.13 to 0.51; P=0.0009; 468 women; five trials; substantial heterogeneity: I(2) = 69%). These findings should be interpreted with caution given the heterogeneity between studies. Comparisons of the effectiveness of black cohosh and other interventions were either inconclusive (because of considerable heterogeneity or an insufficient number of studies) or not statistically significant. Similarly, evidence on the safety of black cohosh was inconclusive, owing to poor reporting. There were insufficient data to pool results for health-related quality of life, sexuality, bone health, vulvovaginal atrophic symptoms and night sweats. No trials reported cost-effectiveness data. The quality of included trials was generally unclear, owing to inadequate reporting.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to support the use of black cohosh for menopausal symptoms. However, there is adequate justification for conducting further studies in this area. The uncertain quality of identified trials highlights the need for improved reporting of study methods, particularly with regards to allocation concealment and the handling of incomplete outcome data. The effect of black cohosh on other important outcomes, such as health-related quality of life, sexuality, bone health, night sweats and cost-effectiveness also warrants further investigation.
Topics: Cimicifuga; Dehydration; Female; Hot Flashes; Humans; Middle Aged; Perimenopause; Phytotherapy; Postmenopause; Randomized Controlled Trials as Topic; Sweating; Trifolium; Vaginal Diseases
PubMed: 22972105
DOI: 10.1002/14651858.CD007244.pub2 -
NIH Consensus and State-of-the-science...To provide health care providers, patients, and the general public with a responsible assessment of currently available data on the management of menopause-related... (Review)
Review
OBJECTIVE
To provide health care providers, patients, and the general public with a responsible assessment of currently available data on the management of menopause-related symptoms.
PARTICIPANTS
A non-DHHS, nonadvocate 12-member panel representing the fields of obstetrics and gynecology, general internal medicine, endocrinology, rheumatology, family and health psychology, geriatric medicine, health services research, demography, biochemistry, epidemiology, clinical research, and biostatistics. In addition, 26 experts in fields related to the conference topic presented data to the panel and to the conference audience.
EVIDENCE
Presentations by experts and a systematic review of the medical literature prepared by the Oregon Evidence-based Practice Center, through the Agency for Healthcare Research and Quality's Evidence-based Practice Centers Program. Scientific evidence was given precedence over clinical anecdotal experience.
CONFERENCE PROCESS
Answering pre-determined questions, the panel drafted its statement based on scientific evidence presented in open forum and on the published scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the audience for comment. The panel then met in executive session to consider the comments received, and released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. A final copy of this statement is available, along with other recent conference statements, at the same web address of http://consensus.nih.gov.
CONCLUSIONS
Menopause is the permanent cessation of menstrual periods that occurs naturally in women, usually in their early 50s. Many women have few or no symptoms; these women are not in need of medical treatment. Premenopausal or perimenopausal women who have menopause induced by surgery, chemotherapy, or radiation are more likely to experience bothersome and even disabling symptoms. These women need safe and effective treatment. It is difficult to differentiate those symptoms that are truly associated with menopause from those due to aging. Hot flashes, night sweats, and vaginal dryness are clearly tied to the menopausal transition, and there is some positive evidence of a menopausal link for sleep disturbance. Vasomotor symptoms are reported with high frequency during the menopausal transition. Estrogen, either by itself or with progestins, is the most consistently effective therapy for these symptoms. However, the Women's Health Initiative (WHI) has identified important risk factors associated with use of these therapies. Decision making for women regarding treatment for menopausal symptoms requires personal knowledge and balancing of these risks. There are many potential alternatives to estrogen. However, their effectiveness and long-term safety need to be studied in rigorous clinical trials in diverse populations of women. Much more research is needed to clearly define the natural history of menopause, associated symptoms, and effectiveness and safety of treatments for bothersome symptoms. Natural histories are important for both science and policy. Knowing how many women transit menopause with few or no symptoms, and how many manage menopause largely on their own, can lead to public health information that empowers women and increases their self-reliance. Medical care and future clinical trials are best focused on women with the most severe and prolonged symptoms. The state of the science in management of menopausal symptoms should be reassessed periodically. Menopause is "medicalized" in contemporary U.S. society. There is great need to develop and disseminate information that emphasizes menopause as a normal, healthy phase of women's lives and promotes its demedicalization. Medical care and future clinical trials are best focused on women with the most severe and prolonged symptoms. Barriers to professional care for these women should be removed.
Topics: Behavior Therapy; Complementary Therapies; Decision Making; Estrogen Replacement Therapy; Evidence-Based Medicine; Female; Hot Flashes; Humans; Interdisciplinary Communication; Menopause; Menopause, Premature; Quality of Life; Risk Assessment; Risk Factors; Sleep Wake Disorders; United States
PubMed: 17308548
DOI: No ID Found -
Canadian Family Physician Medecin de... Jun 1998To review the scientific literature on common alternative remedies for treatment of symptoms attributed to menopause and to contrast this with available lay literature. (Review)
Review
OBJECTIVE
To review the scientific literature on common alternative remedies for treatment of symptoms attributed to menopause and to contrast this with available lay literature.
QUALITY OF EVIDENCE
Scientific articles were identified by searching MEDLINE, CINAHL, and HEALTH databases from 1966 to mid-1997 for English-language articles. More than 200 references were reviewed; 85 were selected for citation based on specific reference to alternative medicine for symptoms commonly attributed to menopause (e.g., hot flashes), to the effects of changing estrogen levels (e.g., irregular menses, vaginal dryness), and to reported side effects of the treatments.
MAIN FINDINGS
The scientific literature was categorized under the headings nutritional supplements, herbal remedies, homeopathic remedies, and physical approaches. Some scientific evidence of the safety and efficacy of alternative treatments during menopause was uncovered, with the strongest evidence emerging in favour of phytoestrogens, which occur in high concentrations as isoflavones in soy products.
CONCLUSIONS
In available controlled studies, the strongest data support phytoestrogens for their role in diminishing menopausal symptoms related to estrogen deficiency and for possible protective effects on bones and the cardiovascular system. Randomized controlled trials, standardization of dosage, and accurate safety and efficacy labeling are required to ensure proper use of alternative remedies.
Topics: Complementary Therapies; Estrogens, Non-Steroidal; Evidence-Based Medicine; Food, Organic; Homeopathy; Humans; Isoflavones; Menopause; Phytoestrogens; Phytotherapy; Plant Preparations; Research Design; Treatment Outcome
PubMed: 9640524
DOI: No ID Found