-
Menopause (New York, N.Y.) Oct 2020Genitourinary syndrome of menopause (GSM) is a chronic, progressive condition frequently manifesting as vaginal dryness and pain with intercourse. Survey data indicate...
IMPORTANCE
Genitourinary syndrome of menopause (GSM) is a chronic, progressive condition frequently manifesting as vaginal dryness and pain with intercourse. Survey data indicate this is a highly prevalent, likely underreported, condition that profoundly affects quality of life for millions of women. Vaginal lasers demonstrate promise as an effective, nonhormone therapeutic alternative for GSM; however, the risks associated with them may have been overstated.
OBJECTIVE
Despite reports of improved sexual and vaginal comfort without serious safety concerns, the Food and Drug Administration (FDA) issued a 2018 safety communication warning against it. We conducted a systematic literature review and surveyed both the FDA Manufacturer and User Facility Device Experience (MAUDE) and Bloomberg Law Databases to evaluate risks associated with laser treatment for GSM.
EVIDENCE REVIEW
A systematic literature review identified articles published before September 2019. The MAUDE database was searched by name from 2009 to 2019 for safety claims for 24 vaginal laser devices. The Bloomberg Law database was searched for product liability claims against any vaginal laser device manufacturer before July 2019.
FINDINGS
Literature review revealed 3 publications detailing 29 presumptive laser-associated complications, only 5 of which (17.2%) reported worsening symptoms after treatment. The MAUDE database contained 120 complaints; only 30 (25%) detailed potential adverse patient events, most frequently pain (n = 12) and burning (n = 10). The Bloomberg law database contained no claims asserting harm from device use.
CONCLUSIONS AND RELEVANCE
Lacking strong evidence indicating significant patient risk for vaginal laser treatment of GSM, the FDA safety communication appears unsubstantiated and implies gender bias. Identified complications suggest most reported "adverse events" represent lack of treatment effect. The well-documented benefits and low risk of adverse event suggest laser therapy for GSM is reasonable with appropriate pretreatment counseling. Additional randomized, well-controlled clinical trials are needed to further elucidate both the safety and efficacy of this nonhormone therapy.
Topics: Communication; Female; Humans; Lasers; Male; Menopause; Quality of Life; Sexism; United States; United States Food and Drug Administration
PubMed: 32796292
DOI: 10.1097/GME.0000000000001577 -
Climacteric : the Journal of the... Oct 2019Ospemifene is a selective estrogen-receptor modulator approved for treating menopause-related moderate to severe dyspareunia and vaginal dryness, symptoms of...
Ospemifene is a selective estrogen-receptor modulator approved for treating menopause-related moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy (VVA), in the United States, and for treating menopause-related, symptomatic VVA in women not appropriate for local estrogen therapy in Europe. This review summarizes the effects of ospemifene on bone, including bone biomarker data from a phase 3 vaginal dryness study. Early-phase studies of postmenopausal women showed that ospemifene dose-dependently decreased bone turnover markers versus placebo, similar to raloxifene. A 12-week, phase 3 study of ospemifene 60 mg/day in postmenopausal women showed improvements in all VVA parameters and significantly greater decreases in seven of nine bone biomarkers versus placebo. Lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤5 years or >5 years) or baseline bone mineral density (BMD) (normal [ = 18], osteopenia [ = 164], or osteoporosis [ 21]). Biomarker studies ( 565 who took ospemifene) therefore support a potential role for ospemifene in maintaining bone health (and possibly reducing fracture risk) in postmenopausal women taking it for VVA; however, caution is warranted because data are limited to biochemical markers, rather than fracture and BMD. Although studies show that bone turnover predicts BMD and fractures, any hypothesis about a bone-sparing effect of ospemifene needs testing in rigorous, long-term, phase 3 studies monitoring fractures and BMD.
Topics: Administration, Oral; Atrophy; Bone Density; Female; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva
PubMed: 31294631
DOI: 10.1080/13697137.2019.1631789 -
The Cochrane Database of Systematic... 2000Endometriosis is a major women's health-care problem. It causes pain and/or infertility, and affects millions of women worldwide. Endometriosis is defined according to... (Review)
Review
BACKGROUND
Endometriosis is a major women's health-care problem. It causes pain and/or infertility, and affects millions of women worldwide. Endometriosis is defined according to histological criteria by the presence of tissue resembling endometrium in sites outside the uterus, most commonly the ovaries and peritoneum. The aim of treatment has been to remove the deposits of ectopic endometrium that are thought to be responsible for the symptoms of endometriosis. This can be achieved surgically by destroying or removing the implants; medical therapies induce atrophy within the hormonally-dependent ectopic endometrium. The duration of hormonal treatment may be limited by unwanted side effects. There is some evidence, however, from epidemiological research that current use of the combined oral contraceptive pill (OCP) is associated with a reduced incidence of endometriosis. The combined pill has the great advantage over other hormonal treatments that it can be taken indefinitely.
OBJECTIVES
The aim of this review was to establish the role of modern oral contraceptives in the management of painful symptoms ascribed to endometriosis.
SEARCH STRATEGY
The search strategy of the Menstrual Disorders Group was utilised to identify all randomised trials of the use of oral contraceptives in the treatment of symptomatic endometriosis. In addition a search of the Cochrane Controlled Trials Register was undertaken together with approaches to pharmaceutical companies.
SELECTION CRITERIA
All truly randomised controlled trials of the use of oral contraceptive pills in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis made visually at a surgical procedure, were included.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction was carried out independently by two reviewers. One of the assessors was an expert in the content matter.
MAIN RESULTS
Only one study was identified which satisfied the inclusion criteria. The oral contraceptive used in a conventional manner was less effective than a GnRH analogue in the relief of dysmenorrhoea. No significant difference was noted between the effectiveness of the oral contraceptive pill and a GnRH analogue in the relief of dyspareunia or non-menstrual pain. Headaches and weight gain were more commonly associated with oral contraceptive usage than with GnRH analogue usage whereas hot flushes, insomnia and vaginal dryness were less common.
REVIEWER'S CONCLUSIONS
There is a paucity of data relating to the use of oral contraceptive preparations in the treatment of symptomtic endometriosis. The data such as it is supports the common practice of the use of the oral contraceptive pill as a first line therapy but further research is required to fully evaluate its role in the management of endometriosis.
Topics: Contraceptives, Oral; Endometriosis; Female; Humans; Pelvic Pain
PubMed: 10796731
DOI: 10.1002/14651858.CD001019 -
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 -
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 -
Oral progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis.American Journal of Obstetrics &... Mar 2019The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other... (Meta-Analysis)
Meta-Analysis
OBJECTIVE DATA
The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other interventions for preterm birth prevention in singleton pregnancies with previous spontaneous preterm birth. The primary outcome was preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth rate at <34 weeks gestation, neonatal morbidity/death, and maternal side-effects.
STUDY
Searches were performed in PubMed, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Register with the use of a combination of words related to "preterm birth," "preterm delivery," "progesterone," "progestogens," and "oral" from inception of each database to April 2018. Additionally, systematic reviews on progesterone for preterm birth prevention that were identified in our search were also reviewed for additional studies. We included all randomized trials of asymptomatic singleton gestations with previous spontaneous singleton preterm birth that had been randomized to prophylactic treatment with oral progesterone vs placebo, no treatment, or other preterm birth intervention. Exclusion criteria included quasirandomized trials, trials that involved women with preterm labor/membrane rupture at the time of randomization or multiple gestations.
STUDY APPRAISAL AND SYNTHESIS METHODS
The risk of bias and quality of evidence were assessed for each study. All analyses were done with an intention-to-treat approach. The primary outcome was incidence of preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth at <34 and <28 weeks gestation, maternal adverse events, maternal serum progesterone level, and neonatal morbidity and death. Summary measures were reported as relative risk or mean difference. I >30% was used to identify heterogeneity.
RESULTS
The search strategy identified 79 distinct studies. Three trials on oral progesterone vs placebo (involved 386 patients: 196 in oral progesterone and 190 in placebo) met the inclusion criteria; there were no studies on oral progesterone vs other intervention that met inclusion criteria. Metaanalysis demonstrated a significantly decreased risk of preterm birth at <37 weeks gestation (42% vs 63%; =.0005; relative risk, 0.68; 95% confidence interval, 0.55-0.84), preterm birth at <34 weeks gestation (29% vs 53%; <.00001; relative risk, 0.55; 95% confidence interval, 0.43-0.71), and increased gestational age of delivery (mean difference, 1.71 weeks; 95% confidence interval, 1.11-2.30) with oral progesterone compared with placebo. There was a significantly lower rate of perinatal death (5% vs 17%; =.001; relative risk 0.32; 95% confidence interval, 0.16-0.63), neonatal intensive care admission (relative risk, 0.39; 95% confidence interval, 0.25-0.61), respiratory distress syndrome (relative risk, 0.21; 95% confidence interval, 0.05-0.93), and higher birthweight (mean difference, 435.06 g; 95% confidence interval, 324.59-545.52) with oral progesterone. There was a higher rate of maternal adverse effects with oral progesterone that included dizziness (relative risk, 2.95; 95% confidence interval, 1.47-5.90), somnolence (relative risk, 2.06; 95% confidence interval, 1.29-3.30), and vaginal dryness (relative risk, 2.37; 95% confidence interval, 1.10-5.11); no serious adverse effects were noted.
CONCLUSION
Oral progesterone appears to be effective for the prevention of recurrent preterm birth and a reduction in perinatal morbidity and mortality rates in asymptomatic singleton gestations with a history of previous spontaneous preterm birth compared with placebo. There were also increased adverse effects with oral progesterone therapy compared with placebo, although none were serious. Further randomized study on oral progesterone compared with other established therapies for the prevention of recurrent preterm birth are warranted.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pregnancy, Multiple; Premature Birth; Progesterone; Progestins
PubMed: 31172132
DOI: 10.1016/j.ajogmf.2019.03.001 -
Gynecologie, Obstetrique, Fertilite &... May 2021Genitourinary menopause syndrome (SGUM) is defined as a set of symptoms associated with a decrease of estrogen and other sexual steroids during menopause. The main...
INTRODUCTION
Genitourinary menopause syndrome (SGUM) is defined as a set of symptoms associated with a decrease of estrogen and other sexual steroids during menopause. The main symptoms are vulvovaginal (dryness, burning, itching), sexual (dyspareunia), and urinary (urinary infections, pollakiuria, nycturia, pain, urinary incontinence by urgenturia). SGUM leads to an alteration of the quality of life, and affects especially women's sexuality.
OBJECTIVE
The objective of this review was to elaborate guidelines for clinical practice regarding the management of SGUM in postmenopausal women, and in particular, in women with a history of breast cancer, treated or not with hormone therapy.
MATERIALS AND METHODS
A systematic review of the literature on SGUM management was conducted on Pubmed, Medline and Cochrane Library. Recommendations from international scholarly societies were also taken into account: International Menopause Society (IMS) https://www.imsociety.org, The North American Menopause Society (NAMS) https://www.menopause.org, Canadian Menopause Society https://www.sigmamenopause.com, European Menopause and Andropause Society (EMAS) https://www.emas-online.org, International Society for the Study of Women's Sexual Health (ISSWSH) https://www.isswsh.org.
RESULTS
Vaginal use of lubricants, moisturizers and hyaluronic acid improves the symptoms of SGUM and may be offered to all patients. For postmenopausal women, local estrogen will be preferred to the oral route because of their safety and efficacy on all symptoms of SGUM during low-dose use. Prasterone is a local treatment that can be proposed as an effective alternative for the management of dyspareunia and sexual function disorder. Current data on oral testosterone, tibolone, oral or transdermal DHEA and herbal medicine are currently limited. Ospemifène, which has shown a significant improvement in sexual symptoms, is not currently marketed in France. In the particular case of women with a history of breast cancer, non-hormonal regimens are a first-line therapy. Current data on the risk of breast cancer recurrence when administering low-dose local estrogen are reassuring but do not support a conclusion that this treatment is safe.
CONCLUSION
SGUM is a common symptom that can affect the quality of life of postmenopausal women. A treatment should be systematically proposed. Local non-hormonal treatment may be offered in all women. Local low-dose estrogen therapy and Prasterone has shown an interest in the management of symptoms. In women before a history of breast cancer, local non-hormonal treatment should be offered first-line. The safety of low-dose local estrogen therapy and Prasterone cannot be established at this time. Other alternatives exist but are not currently recommended in France due to lack of data.
Topics: Atrophy; Canada; Female; Humans; Menopause; Postmenopause; Quality of Life; Vagina
PubMed: 33757926
DOI: 10.1016/j.gofs.2021.03.025 -
Sexual Medicine Reviews Jan 2020The puerperium is a period of adaptation in which various transformations take place in the lives of women and men on their way to becoming mothers and fathers. These...
INTRODUCTION
The puerperium is a period of adaptation in which various transformations take place in the lives of women and men on their way to becoming mothers and fathers. These changes can also have repercussions on their sexual relations. How the couple deals with this transition is crucial to the well-being of the couple and affects how parents relate to the baby.
AIM
This study aimed to explore the factors that influence sexuality in both women and men during postpartum.
METHODS
We conducted a bibliographic review of 236 articles found on the PubMed database and published from 2008 to January 2019.
MAIN OUTCOME MEASURE
The main outcome measure was the impact of various physical, psychological, and sociocultural factors on couples' sexual functioning during postpartum.
RESULTS
The main problems that couples face after childbirth can be classified as (i) psychological changes, such as loss of a sense of self, transitioning to parenthood, taking on the new roles of mother and father, and feelings of abandonment among men; (ii) body changes in women that affect their self-image and perineal trauma; (iii) hormonal changes in women and men that can lead to reduced sexual desire in both and vaginal dryness or dyspareunia in women; (iv) changes in the marital relationship, including changes in each other's roles, taking time for intimacy, and initiating sexual intercourse; (v) sociocultural influences, such as social support, culturally expected roles, and beliefs regarding when to resume sex; and (vi) lifestyle changes, especially with regard to baby care.
CONCLUSION
Sexuality during postpartum is influenced by multiple factors: physical, psychological, and sociocultural. Our findings offer a deeper understanding of how the transition to parenthood affects sexual relationships during the postpartum period. Implications regarding caring for and promoting the sexual health of individuals and couples after childbirth are discussed, and some medical recommendations for parents are offered. Serrano Drozdowskyj E, Gimeno Castro E, Trigo López E, et al. Factors Influencing Couples' Sexuality in the Puerperium: A Systematic Review. Sex Med Rev 2020;8:38-47.
Topics: Dyspareunia; Female; Humans; Libido; Male; Postpartum Period; Sexual Behavior
PubMed: 31447412
DOI: 10.1016/j.sxmr.2019.07.002 -
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 -
Menopause (New York, N.Y.) May 2022Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous...
IMPORTANCE
Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous studies have addressed treatment options for sexual dysfunction in women with cancer, but it still remains a challenge to select the most efficacious option for patients.
OBJECTIVE
To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors.
EVIDENCE REVIEW
A literature search of the electronic databases MEDLINE, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) was conducted using general search terms of "women", "cancer", "intervention", "sexual dysfunction". We included randomized controlled trials (RCTs) and uncontrolled before-after studies that evaluated the efficacy of intervention for female sexual dysfunction in women with history of cancer. Methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies.
FINDINGS
Thirty-six studies were included for qualitative synthesis (14 RCTs (n = 1284), 17 uncontrolled trials (n = 589), and 5 cohort studies (n = 497). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intravaginal dehydroepiandrosterone (DHEA) (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements of sexual function. Both laser therapy (fractional CO2 and erbium) and multimodal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function.
CONCLUSIONS AND RELEVANCE
The most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multimodal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10-70 participants), with moderate to high risk of bias. Therefore, large-scale, double-blind, RCTs with long-period follow-up, and at low risk of bias are needed to show efficacy for these interventions.
Topics: Cancer Survivors; Dehydroepiandrosterone; Dyspareunia; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; United States; Vaginal Creams, Foams, and Jellies; Vaginal Diseases
PubMed: 35486951
DOI: 10.1097/GME.0000000000001953