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Sexual Medicine Reviews Apr 2022Hypertonicity of the pelvic floor (PFH) is a disabling condition with urological, gynecological and gastrointestinal symptoms, sexual problems and chronic pelvic pain,... (Review)
Review
INTRODUCTION
Hypertonicity of the pelvic floor (PFH) is a disabling condition with urological, gynecological and gastrointestinal symptoms, sexual problems and chronic pelvic pain, impacting quality of life. Pelvic floor physical therapy (PFPT) is a first-line intervention, yet no systematic review on the efficacy of PFPT for the treatment of PFH has been conducted.
OBJECTIVES
To systematically appraise the current literature on efficacy of PFPT modalities related to PFH.
METHODS
PubMed, Embase, Emcare, Web of Science, and Cochrane databases were searched from inception until February 2020. A manual search from reference lists of included articles was performed. Ongoing trials were reviewed using clinicaltrial.gov. Randomized controlled trials (RCTs), prospective - and retrospective cohorts and case-study analyses were included. Outcome measures were pelvic floor muscle tone and function, pain reports, sexual function, pelvic floor symptom scores, quality of life and patients' perceived effect.
RESULTS
The literature search resulted in 10 eligible studies including 4 RCTs, 5 prospective studies, and 1 case study published between 2000 and 2019. Most studies had a high risk of bias associated with the lack of a comparison group, insufficient sample sizes and non-standardized interventions. Six studies were of low and 4 of medium quality. All studies were narratively reviewed. Three of 4 RCTs found positive effects of PFPT compared to controls on five out of 6 outcome measures. The prospective studies found significant improvements in all outcome measures that were assessed. PFPT seems to be efficacious in patients with chronic prostatitis, chronic pelvic pain syndrome, vulvodynia, and dyspareunia. Smallest effects were seen in patients with interstitial cystitis and painful bladder syndrome.
CONCLUSION
The findings of this systematic review suggest that PFPT can be beneficial in patients with PFH. Further high-quality RCTs should be performed to confirm the effectiveness of PFPT in the treatment of PFH. van Reijn-Baggen DA, Han-Geurts IJM, Voorham-van der Zalm PJ, et al. Pelvic Floor Physical Therapy for Pelvic Floor Hypertonicity: A Systematic Review of Treatment Efficacy. Sex Med Rev 2022;10:209-230.
Topics: Female; Humans; Male; Pelvic Floor; Pelvic Floor Disorders; Pelvic Pain; Physical Therapy Modalities; Treatment Outcome
PubMed: 34127429
DOI: 10.1016/j.sxmr.2021.03.002 -
BMC Women's Health Jul 2023Dyspareunia is defined as the occurrence of pain during or after sexual intercourse, which directly affects physical, sexual, and mental health. This condition can lead... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyspareunia is defined as the occurrence of pain during or after sexual intercourse, which directly affects physical, sexual, and mental health. This condition can lead to depression, anxiety, and low self-esteem in women who experience it.
OBJECTIVES
The aim of this research was to evaluate the effectiveness of physical therapy interventions for the treatment of female dyspareunia.
DESIGN
A systematic review and meta-analysis was conducted.
METHOD
Search of publications was conducted in Scopus, Medline, Pubmed, Cinahl and Web of Science. Treatment effects were defined as standardized mean difference and their 95% confidence intervals. Statistical heterogeneity was assessed using Crohan's Q test and quantified using the I index.
RESULTS
Of the 19 articles selected, six applied multimodal physiotherapy treatments; five, electrotherapy; three, Thiele's massage; two, interdisciplinary interventions or pelvic floor muscle training; and one, extracorporeal shockwave therapy. The meta-analysis showed significant results for the variables pain and quality of life with the interventions based on electrotherapy and electrotherapy combined with pelvic floor muscle training. These interventions did not show significant results for the improvement of sexual function.
CONCLUSIONS
Physiotherapy techniques are effective and procedures have been identified with reliable results in improving pain and quality of life in patients with dyspareunia. One of the most important aspects is the strengthening of the perineal musculature and the application of Transcutaneous Electrical Nerve Stimulation. Furthermore, manual trigger point release therapy and Thiele massage, optimize and guarantee the reduction of pain intensity.
PROSPERO REGISTRATION
CRD42021236155.
Topics: Humans; Female; Dyspareunia; Quality of Life; Physical Therapy Modalities; Pain; Transcutaneous Electric Nerve Stimulation
PubMed: 37482613
DOI: 10.1186/s12905-023-02532-8 -
Reproductive Biology and Endocrinology... Aug 2023This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain.
METHODS
A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
RESULTS
A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation.
CONCLUSIONS
The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain.
TRIAL REGISTRATION
PROSPERO registration number: CRD42023415198.
Topics: Female; Humans; Antioxidants; Pelvic Pain; Vitamins; Endometriosis; Vitamin A; Ascorbic Acid; Vitamin K; Dietary Supplements
PubMed: 37644533
DOI: 10.1186/s12958-023-01126-1 -
The Cochrane Database of Systematic... Jan 2009Episiotomy is done to prevent severe perineal tears, but its routine use has been questioned. The relative effects of midline compared with midlateral episiotomy are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Episiotomy is done to prevent severe perineal tears, but its routine use has been questioned. The relative effects of midline compared with midlateral episiotomy are unclear.
OBJECTIVES
The objective of this review was to assess the effects of restrictive use of episiotomy compared with routine episiotomy during vaginal birth.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2008).
SELECTION CRITERIA
Randomized trials comparing restrictive use of episiotomy with routine use of episiotomy; restrictive use of mediolateral episiotomy versus routine mediolateral episiotomy; restrictive use of midline episiotomy versus routine midline episiotomy; and use of midline episiotomy versus mediolateral episiotomy.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial quality and extracted the data.
MAIN RESULTS
We included eight studies (5541 women). In the routine episiotomy group, 75.15% (2035/2708) of women had episiotomies, while the rate in the restrictive episiotomy group was 28.40% (776/2733). Compared with routine use, restrictive episiotomy resulted in less severe perineal trauma (relative risk (RR) 0.67, 95% confidence interval (CI) 0.49 to 0.91), less suturing (RR 0.71, 95% CI 0.61 to 0.81) and fewer healing complications (RR 0.69, 95% CI 0.56 to 0.85). Restrictive episiotomy was associated with more anterior perineal trauma (RR 1.84, 95% CI 1.61 to 2.10). There was no difference in severe vaginal/perineal trauma (RR 0.92, 95% CI 0.72 to 1.18); dyspareunia (RR 1.02, 95% CI 0.90 to 1.16); urinary incontinence (RR 0.98, 95% CI 0.79 to 1.20) or several pain measures. Results for restrictive versus routine mediolateral versus midline episiotomy were similar to the overall comparison.
AUTHORS' CONCLUSIONS
Restrictive episiotomy policies appear to have a number of benefits compared to policies based on routine episiotomy. There is less posterior perineal trauma, less suturing and fewer complications, no difference for most pain measures and severe vaginal or perineal trauma, but there was an increased risk of anterior perineal trauma with restrictive episiotomy.
Topics: Episiotomy; Female; Humans; Parturition; Perineum; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 19160176
DOI: 10.1002/14651858.CD000081.pub2 -
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 -
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 -
Journal of Gynecology Obstetrics and... Oct 2023Natural childbirth is associated with the risk of damage to the perineum - a tears or a episiotomy. Adequate preparation of the woman for childbirth is essential to... (Review)
Review
BACKGROUND
Natural childbirth is associated with the risk of damage to the perineum - a tears or a episiotomy. Adequate preparation of the woman for childbirth is essential to minimize the occurrence of perinatal injuries.
AIM
The aim of the review is to assess and analyze the impact of APM (antental perineal massage) on perinatal perineal injuries and the development of pelvic pain and other complications in postpartum women, such as dyspareunia, urinary (UI), gas (GI), and fecal incontinence (FI).
METHODS
PubMed, Web of Science, Scopus and Embase were searched. Three authors independently searched databases and selected articles for inclusion and exclusion criteria. Next one author did Risk of Bias 2 and ROBINS 1 analyze.
FINDINGS
Of 711 articles, 18 publications were left for the review. All 18 studies examined the risk of perineal injuries (tearing and episiotomy), 7 pain in postpartum period, 6 postpartum urinary, gas/fecal incontinence and 2 described dyspareunia. Most authors described APM from 34 weeks of pregnancy until delivery. There were different techniques and times for doing APM procedures.
DISCUSSION
APM has many benefits for women during labor and the postpartum period (e.g. lower rate of perineal injuries and pain). However, it can be observed that individual publications differ from each other in the time of massage, the period and frequency of its performance, the form of obtaining instruction and control of patients. These components may affect the results obtained.
CONCLUSION
APM can protects the perineum from injuries during labor. It also reduces risk of fecal and gas incontinence in postpartum period.
Topics: Pregnancy; Female; Humans; Perineum; Fecal Incontinence; Dyspareunia; Parturition; Massage; Pelvic Pain; Urinary Incontinence
PubMed: 37414371
DOI: 10.1016/j.jogoh.2023.102627 -
The Cochrane Database of Systematic... Feb 2017Some clinicians believe that routine episiotomy, a surgical cut of the vagina and perineum, will prevent serious tears during childbirth. On the other hand, an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some clinicians believe that routine episiotomy, a surgical cut of the vagina and perineum, will prevent serious tears during childbirth. On the other hand, an episiotomy guarantees perineal trauma and sutures.
OBJECTIVES
To assess the effects on mother and baby of a policy of selective episiotomy ('only if needed') compared with a policy of routine episiotomy ('part of routine management') for vaginal births.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (14 September 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing selective versus routine use of episiotomy, irrespective of parity, setting or surgical type of episiotomy. We included trials where either unassisted or assisted vaginal births were intended. Quasi-RCTs, trials using a cross-over design or those published in abstract form only were not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies, extracted data, and assessed risk of bias. A third author mediated where there was no clear consensus. We observed good practice for data analysis and interpretation where trialists were review authors. We used fixed-effect models unless heterogeneity precluded this, expressed results as risk ratios (RR) and 95% confidence intervals (CI), and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
This updated review includes 12 studies (6177 women), 11 in women in labour for whom a vaginal birth was intended, and one in women where an assisted birth was anticipated. Two were trials each with more than 1000 women (Argentina and the UK), and the rest were smaller (from Canada, Germany, Spain, Ireland, Malaysia, Pakistan, Columbia and Saudi Arabia). Eight trials included primiparous women only, and four trials were in both primiparous and multiparous women. For risk of bias, allocation was adequately concealed and reported in nine trials; sequence generation random and adequately reported in three trials; blinding of outcomes adequate and reported in one trial, blinding of participants and personnel reported in one trial.For women where an unassisted vaginal birth was anticipated, a policy of selective episiotomy may result in 30% fewer women experiencing severe perineal/vaginal trauma (RR 0.70, 95% CI 0.52 to 0.94; 5375 women; eight RCTs; low-certainty evidence). We do not know if there is a difference for blood loss at delivery (an average of 27 mL less with selective episiotomy, 95% CI from 75 mL less to 20 mL more; two trials, 336 women, very low-certainty evidence). Both selective and routine episiotomy have little or no effect on infants with Apgar score less than seven at five minutes (four trials, no events; 3908 women, moderate-certainty evidence); and there may be little or no difference in perineal infection (RR 0.90, 95% CI 0.45 to 1.82, three trials, 1467 participants, low-certainty evidence).For pain, we do not know if selective episiotomy compared with routine results in fewer women with moderate or severe perineal pain (measured on a visual analogue scale) at three days postpartum (RR 0.71, 95% CI 0.48 to 1.05, one trial, 165 participants, very low-certainty evidence). There is probably little or no difference for long-term (six months or more) dyspareunia (RR1.14, 95% CI 0.84 to 1.53, three trials, 1107 participants, moderate-certainty evidence); and there may be little or no difference for long-term (six months or more) urinary incontinence (average RR 0.98, 95% CI 0.67 to 1.44, three trials, 1107 participants, low-certainty evidence). One trial reported genital prolapse at three years postpartum. There was no clear difference between the two groups (RR 0.30, 95% CI 0.06 to 1.41; 365 women; one trial, low certainty evidence). Other outcomes relating to long-term effects were not reported (urinary fistula, rectal fistula, and faecal incontinence). Subgroup analyses by parity (primiparae versus multiparae) and by surgical method (midline versus mediolateral episiotomy) did not identify any modifying effects. Pain was not well assessed, and women's preferences were not reported.One trial examined selective episiotomy compared with routine episiotomy in women where an operative vaginal delivery was intended in 175 women, and did not show clear difference on severe perineal trauma between the restrictive and routine use of episiotomy, but the analysis was underpowered.
AUTHORS' CONCLUSIONS
In women where no instrumental delivery is intended, selective episiotomy policies result in fewer women with severe perineal/vaginal trauma. Other findings, both in the short or long term, provide no clear evidence that selective episiotomy policies results in harm to mother or baby.The review thus demonstrates that believing that routine episiotomy reduces perineal/vaginal trauma is not justified by current evidence. Further research in women where instrumental delivery is intended may help clarify if routine episiotomy is useful in this particular group. These trials should use better, standardised outcome assessment methods.
Topics: Apgar Score; Blood Loss, Surgical; Dyspareunia; Episiotomy; Female; Humans; Pain Measurement; Parity; Parturition; Perineum; Pregnancy; Randomized Controlled Trials as Topic; Surgical Wound Infection; Urinary Incontinence
PubMed: 28176333
DOI: 10.1002/14651858.CD000081.pub3 -
Pharmaceuticals (Basel, Switzerland) Apr 2023(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can... (Review)
Review
(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.
PubMed: 37111307
DOI: 10.3390/ph16040550 -
The Cochrane Database of Systematic... Oct 2016Tibolone is a synthetic steroid used for the treatment of menopausal symptoms, on the basis of short-term data suggesting its efficacy. We considered the balance between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tibolone is a synthetic steroid used for the treatment of menopausal symptoms, on the basis of short-term data suggesting its efficacy. We considered the balance between the benefits and risks of tibolone.
OBJECTIVES
To evaluate the effectiveness and safety of tibolone for treatment of postmenopausal and perimenopausal women.
SEARCH METHODS
In October 2015, we searched the Gynaecology and Fertility Group (CGF) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO (from inception), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinicaltrials.gov. We checked the reference lists in articles retrieved.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing tibolone versus placebo, oestrogens and/or combined hormone therapy (HT) in postmenopausal and perimenopausal women.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures of The Cochrane Collaboration. Primary outcomes were vasomotor symptoms, unscheduled vaginal bleeding and long-term adverse events. We evaluated safety outcomes and bleeding in studies including women either with or without menopausal symptoms.
MAIN RESULTS
We included 46 RCTs (19,976 women). Most RCTs evaluated tibolone for treating menopausal vasomotor symptoms. Some had other objectives, such as assessment of bleeding patterns, endometrial safety, bone health, sexuality and safety in women with a history of breast cancer. Two included women with uterine leiomyoma or lupus erythematosus. Tibolone versus placebo Vasomotor symptomsTibolone was more effective than placebo (standard mean difference (SMD) -0.99, 95% confidence interval (CI) -1.10 to -0.89; seven RCTs; 1657 women; moderate-quality evidence), but removing trials at high risk of attrition bias attenuated this effect (SMD -0.61, 95% CI -0.73 to -0.49; odds ratio (OR) 0.33, 85% CI 0.27 to 0.41). This suggests that if 67% of women taking placebo experience vasomotor symptoms, between 35% and 45% of women taking tibolone will do so. Unscheduled bleedingTibolone was associated with greater likelihood of bleeding (OR 2.79, 95% CI 2.10 to 3.70; nine RCTs; 7814 women; I = 43%; moderate-quality evidence). This suggests that if 18% of women taking placebo experience unscheduled bleeding, between 31% and 44% of women taking tibolone will do so. Long-term adverse eventsMost of the studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Breast cancerWe found no evidence of differences between groups among women with no history of breast cancer (OR 0.52, 95% CI 0.21 to 1.25; four RCTs; 5500 women; I= 17%; very low-quality evidence). Among women with a history of breast cancer, tibolone was associated with increased risk (OR 1.5, 95% CI 1.21 to 1.85; two RCTs; 3165 women; moderate-quality evidence). Cerebrovascular eventsWe found no conclusive evidence of differences between groups in cerebrovascular events (OR 1.74, 95% CI 0.99 to 3.04; four RCTs; 7930 women; I = 0%; very low-quality evidence). We obtained most data from a single RCT (n = 4506) of osteoporotic women aged 60 to 85 years, which was stopped prematurely for increased risk of stroke. Other outcomesEvidence on other outcomes was of low or very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows:• Endometrial cancer: OR 2.04, 95% CI 0.79 to 5.24; nine RCTs; 8504 women; I = 0%.• Cardiovascular events: OR 1.38, 95% CI 0.84 to 2.27; four RCTs; 8401 women; I = 0%.• Venous thromboembolic events: OR 0.85, 95% CI 0.37 to 1.97; 9176 women; I = 0%.• Mortality from any cause: OR 1.06, 95% CI 0.79 to 1.41; four RCTs; 8242 women; I = 0%. Tibolone versus combined HT Vasomotor symptomsCombined HT was more effective than tibolone (SMD 0.17, 95% CI 0.06 to 0.28; OR 1.36, 95% CI 1.11 to 1.66; nine studies; 1336 women; moderate-quality evidence). This result was robust to a sensitivity analysis that excluded trials with high risk of attrition bias, suggesting a slightly greater disadvantage of tibolone (SMD 0.25, 95% CI 0.09 to 0.41; OR 1.57, 95% CI 1.18 to 2.10). This suggests that if 7% of women taking combined HT experience vasomotor symptoms, between 8% and 14% of women taking tibolone will do so. Unscheduled bleedingTibolone was associated with a lower rate of bleeding (OR 0.32, 95% CI 0.24 to 0.41; 16 RCTs; 6438 women; I = 72%; moderate-quality evidence). This suggests that if 47% of women taking combined HT experience unscheduled bleeding, between 18% and 27% of women taking tibolone will do so. Long-term adverse eventsMost studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Evidence was of very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows:• Endometrial cancer: OR 1.47, 95% CI 0.23 to 9.33; five RCTs; 3689 women; I = 0%.• Breast cancer: OR 1.69, 95% CI 0.78 to 3.67; five RCTs; 4835 women; I = 0%.• Venous thromboembolic events: OR 0.44, 95% CI 0.09 to 2.14; four RCTs; 4529 women; I = 0%.• Cardiovascular events: OR 0.63, 95% CI 0.24 to 1.66; two RCTs; 3794 women; I = 0%.• Cerebrovascular events: OR 0.76, 95% CI 0.16 to 3.66; four RCTs; 4562 women; I = 0%.• Mortality from any cause: only one event reported (two RCTs; 970 women).
AUTHORS' CONCLUSIONS
Moderate-quality evidence suggests that tibolone is more effective than placebo but less effective than HT in reducing menopausal vasomotor symptoms, and that tibolone is associated with a higher rate of unscheduled bleeding than placebo but with a lower rate than HT.Compared with placebo, tibolone increases recurrent breast cancer rates in women with a history of breast cancer, and may increase stroke rates in women over 60 years of age. No evidence indicates that tibolone increases the risk of other long-term adverse events, or that it differs from HT with respect to long-term safety.Much of the evidence was of low or very low quality. Limitations included high risk of bias and imprecision. Most studies were financed by drug manufacturers or failed to disclose their funding source.
Topics: Aged; Breast Neoplasms; Dyspareunia; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Middle Aged; Neoplasm Recurrence, Local; Norpregnenes; Postmenopause; Randomized Controlled Trials as Topic; Stroke; Sweating; Uterine Hemorrhage
PubMed: 27733017
DOI: 10.1002/14651858.CD008536.pub3