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The Cochrane Database of Systematic... May 2022Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
OBJECTIVES
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
METHODS
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty). We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
MAIN RESULTS
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows. First-line treatments Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD -105.71 mL/cycle, 95% CI -201.10 to -10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD -80.32 mL/cycle, 95% CI -127.67 to -32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD -76.93 mL/cycle, 95% CI -153.82 to -0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD -40.67 mL/cycle, -84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty. We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction. Second-line treatments Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence). Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).
AUTHORS' CONCLUSIONS
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Topics: Amenorrhea; Antifibrinolytic Agents; Child, Preschool; Female; Humans; Menorrhagia; Network Meta-Analysis; Progestins; Quality of Life; Systematic Reviews as Topic
PubMed: 35638592
DOI: 10.1002/14651858.CD013180.pub2 -
Journal of Minimally Invasive Gynecology May 2022To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence.
DATA SOURCES
The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021.
METHODS OF STUDY SELECTION
Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence.
TABULATION, INTEGRATION, AND RESULTS
Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls.
CONCLUSION
In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.
Topics: Contraceptives, Oral, Combined; Endometriosis; Female; Humans; Network Meta-Analysis; Ovariectomy; Postoperative Period
PubMed: 35123042
DOI: 10.1016/j.jmig.2021.11.024 -
European Journal of Obstetrics,... Apr 2020Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear.
OBJECTIVE
To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review.
SEARCH STRATEGY
Literature search conducted in databases from January 1990 till August 2019 using various search terms.
SELECTION CRITERIA
Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language.
DATA COLLECTION AND ANALYSIS
PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer.
RESULTS
Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively.
CONCLUSION
OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.
Topics: Adenocarcinoma; Contraceptives, Oral; Female; Humans; Risk; Uterine Cervical Neoplasms
PubMed: 32114321
DOI: 10.1016/j.ejogrb.2020.02.014 -
The Cochrane Database of Systematic... Sep 2021Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first... (Review)
Review
BACKGROUND
Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first published in 2015 focusing on the use of glutamate receptor modulators in unipolar depression.
OBJECTIVES
To assess the effects - and review the acceptability and tolerability - of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with unipolar major depressive disorder.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020. We did not apply any restrictions to date, language or publication status.
SELECTION CRITERIA
Double- or single-blinded randomised controlled trials (RCTs) comparing ketamine, memantine, esketamine or other glutamate receptor modulators with placebo (pill or saline infusion), other active psychotropic drugs, or electroconvulsive therapy (ECT) in adults with unipolar major depression.
DATA COLLECTION AND ANALYSIS
Three review authors independently identified studies, assessed trial quality and extracted data. The primary outcomes were response rate (50% reduction on a standardised rating scale) and adverse events. We decided a priori to measure the efficacy outcomes at different time points and run sensitivity/subgroup analyses. Risk of bias was assessed using the Cochrane tool, and certainty of the evidence was assessed using GRADE.
MAIN RESULTS
Thirty-one new studies were identified for inclusion in this updated review. Overall, we included 64 studies (5299 participants) on ketamine (31 trials), esketamine (9), memantine (5), lanicemine (4), D-cycloserine (2), Org26576 (2), riluzole (2), atomoxetine (1), basimglurant (1), citicoline (1), CP-101,606 (1), decoglurant (1), MK-0657 (1), N-acetylcysteine (1), rapastinel (1), and sarcosine (1). Forty-eight studies were placebo-controlled, and 48 were two-arm studies. The majority of trials defined an inclusion criterion for the severity of depressive symptoms at baseline: 29 at least moderate depression; 17 severe depression; and five mild-to-moderate depression. Nineteen studies recruited only patients with treatment-resistant depression, defined as inadequate response to at least two antidepressants. The majority of studies investigating ketamine administered as a single dose, whilst all of the included esketamine studies used a multiple dose regimen (most frequently twice a week for four weeks). Most studies looking at ketamine used intravenous administration, whilst the majority of esketamine trials used intranasal routes. The evidence suggests that ketamine may result in an increase in response and remission compared with placebo at 24 hours odds ratio (OR) 3.94, 95% confidence interval (CI) 1.54 to 10.10; n = 185, studies = 7, very low-certainty evidence). Ketamine may reduce depression rating scale scores over placebo at 24 hours, but the evidence is very uncertain (standardised mean difference (SMD) -0.87, 95% CI -1.26 to -0.48; n = 231, studies = 8, very low-certainty evidence). There was no difference in the number of participants assigned to ketamine or placebo who dropped out for any reason (OR 1.25, 95% CI 0.19 to 8.28; n = 201, studies = 6, very low-certainty evidence). When compared with midazolam, the evidence showed that ketamine increases remission rates at 24 hours (OR 2.21, 95% CI 0.67 to 7.32; n = 122,studies = 2, low-certainty evidence). The evidence is very uncertain about the response efficacy of ketamine at 24 hours in comparison with midazolam, and its ability to reduce depression rating scale scores at the same time point (OR 2.48, 95% CI 1.00 to 6.18; n = 296, studies = 4,very low-certainty evidence). There was no difference in the number of participants who dropped out of studies for any reason between ketamine and placebo (OR 0.33, 95% CI 0.05 to 2.09; n = 72, studies = 1, low-certainty evidence). Esketamine treatment likely results in a large increase in participants achieving remission at 24 hours compared with placebo (OR 2.74, 95% CI 1.71 to 4.40; n = 894, studies = 5, moderate-certainty evidence). Esketamine probably results in decreases in depression rating scale scores at 24 hours compared with placebo (SMD -0.31, 95% CI -0.45 to -0.17; n = 824, studies = 4, moderate-certainty evidence). Our findings show that esketamine increased response rates, although this evidence is uncertain (OR 2.11, 95% CI 1.20 to 3.68; n = 1071, studies = 5, low-certainty evidence). There was no evidence that participants assigned to esketamine treatment dropped out of trials more frequently than those assigned to placebo for any reason (OR 1.58, 95% CI 0.92 to 2.73; n = 773, studies = 4,moderate-certainty evidence). We found very little evidence for the remaining glutamate receptor modulators. We rated the risk of bias as low or unclear for most domains, though lack of detail regarding masking of treatment in the studies reduced our certainty in the effect for all outcomes.
AUTHORS' CONCLUSIONS
Our findings show that ketamine and esketamine may be more efficacious than placebo at 24 hours. How these findings translate into clinical practice, however, is not entirely clear. The evidence for use of the remaining glutamate receptor modulators is limited as very few trials were included in the meta-analyses for each comparison and the majority of comparisons included only one study. Long term non-inferiority RCTs comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy.
Topics: Adult; Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Ketamine; Receptors, Glutamate
PubMed: 34510411
DOI: 10.1002/14651858.CD011612.pub3 -
Physical Therapy Oct 2019Dysmenorrhea is a health problem with a high impact on health and society. Some drugs have been shown to be effective at treating dysmenorrhea. Therapeutic exercise is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dysmenorrhea is a health problem with a high impact on health and society. Some drugs have been shown to be effective at treating dysmenorrhea. Therapeutic exercise is another option for reducing the symptomatology of this health problem, with a low cost and the absence of side effects.
PURPOSE
The purposes of this review were to study the efficacy of physical exercise for pain intensity in primary dysmenorrhea and to assess its effectiveness in decreasing the duration of pain and improving quality of life.
DATA SOURCES
Searches were conducted between February 2017 and May 2017 in the databases Web of Science, Physiotherapy Evidence Database (PEDro), PubMed, Scopus, CINAHL, and Dialnet, using the terms dysmenorrhea, exercise therapy, exercise movement technique, exercise, physical therapy, physical therapy speciality, treatment, primary dysmenorrhea, prevention, etiology, epidemiology, and pain.
STUDY SELECTION
We included randomized controlled trial studies conducted on women who were 16 to 25 years old and had primary dysmenorrhea, studies that included exercise as a type of therapy, studies that assessed the intensity and duration of pain and quality of life, and studies published in English or Spanish. Studies that included women with irregular cycles, women diagnosed with a gynecological disease, women who had had surgery, women with serious diseases, or women who used intracavitary or oral contraceptives were excluded. We started with 455 studies; 16 were included in the systematic review, and 11 were included in the 3 meta-analyses that were carried out.
DATA EXTRACTION
Two authors selected the studies and extracted their characteristics (participants, intervention, comparators, and outcomes) and results. The evaluation of the methodological quality of the studies was carried out by PEDro scale.
DATA SYNTHESIS
There was moderate evidence that therapeutic exercise can be considered a useful tool in the treatment of primary dysmenorrhea in terms of a reduction in pain intensity. Regarding the duration of pain and quality of life, there was low evidence and very low evidence, respectively. In the 3 meta-analyses, the results were significantly positive in favor of exercise for decreases in both the intensity and the duration of pain.
LIMITATIONS
Limitations of this study include the great heterogeneity of the interventions applied in the studies in terms of type of exercise, in combination or alone, and dosage. This review includes a small number of studies with risk of bias, so the present findings must be interpreted with caution.
CONCLUSIONS
Therapeutic exercise reduces pain intensity in patients with primary dysmenorrhea.
Topics: Dysmenorrhea; Exercise Therapy; Female; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31665789
DOI: 10.1093/ptj/pzz101 -
Contraception Mar 2022Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the...
OBJECTIVE
Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection.
STUDY DESIGN
Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725).
RESULTS
Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association.
CONCLUSION
We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk.
IMPLICATIONS
Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
Topics: Contraceptives, Oral, Hormonal; Female; Hormonal Contraception; Humans; Papillomavirus Infections; Progestins; Prospective Studies; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 34752778
DOI: 10.1016/j.contraception.2021.10.018 -
Orvosi Hetilap Nov 2023Emergency contraception is an effective and safe solution for preventing unwanted pregnancies. Many methods of emergency contraception are used, which have different...
INTRODUCTION
Emergency contraception is an effective and safe solution for preventing unwanted pregnancies. Many methods of emergency contraception are used, which have different mechanisms of action and time frames.
OBJECTIVE
Providing information to healthcare professionals and decision-makers based on the literature data about the target populations of emergency contraception, evidence-based modern methods, their effectiveness, and practical application for the purpose of reducing the incidence of unintended pregnancies.
METHODS
We conducted a systematic literature search in MEDLINE (PubMed), Embase and Scopus databases based on relevant keywords, for publications that were published between 1960 and 2023.
RESULTS
23 clinical professional publications were selected that examined the effectiveness of oral and long-term usable contraceptives as emergency contraceptives. Our research results were interpreted in terms of weight, breastfeeding, time elapsed since the intercourse and future contraceptive plans, which help to select the most appropriate emergency contraceptive for healthcare professionals.
CONCLUSION
Based on the literature data, our systematic review provides assistance for choosing between the available oral levonorgestrel, ulipristal acetate, and intrauterine contraceptive devices available in Hungary based on effectiveness, target population, and accessibility. We support the healthcare governance in creating up-to-date professional guidelines to improve the availability of emergency contraception and, consequently, enhance reproductive health. Orv Hetil. 2023; 164(44): 1736-1748.
Topics: Female; Pregnancy; Humans; Contraception, Postcoital; Databases, Factual; Health Personnel; Hungary
PubMed: 37930357
DOI: 10.1556/650.2023.32757 -
Sports Medicine (Auckland, N.Z.) Jan 2024Resistance exercise training is widely used by general and athletic populations to increase skeletal muscle hypertrophy, power and strength. Endogenous sex hormones... (Meta-Analysis)
Meta-Analysis
The Effect of Hormonal Contraceptive Use on Skeletal Muscle Hypertrophy, Power and Strength Adaptations to Resistance Exercise Training: A Systematic Review and Multilevel Meta-analysis.
BACKGROUND
Resistance exercise training is widely used by general and athletic populations to increase skeletal muscle hypertrophy, power and strength. Endogenous sex hormones influence various bodily functions, including possibly exercise performance, and may influence adaptive changes in response to exercise training. Hormonal contraceptive (HC) use modulates the profile of endogenous sex hormones, and therefore, there is increasing interest in the impact, if any, of HC use on adaptive responses to resistance exercise training.
OBJECTIVE
Our aim is to provide a quantitative synthesis of the effect of HC use on skeletal muscle hypertrophy, power and strength adaptations in response to resistance exercise training.
METHODS
A systematic review with meta-analysis was conducted on experimental studies which directly compared skeletal muscle hypertrophy, power and strength adaptations following resistance exercise training in hormonal contraceptive users and non-users conducted before July 2023. The search using the online databases PUBMED, SPORTDiscus, Web of Science, Embase and other supplementary search strategies yielded 4669 articles, with 8 articles (54 effects and 325 participants) meeting the inclusion criteria. The methodological quality of the included studies was assessed using the "Tool for the assessment of study quality and reporting in exercise".
RESULTS
All included studies investigated the influence of oral contraceptive pills (OCP), with no study including participants using other forms of HC. The articles were analysed using a meta-analytic multilevel maximum likelihood estimator model. The results indicate that OCP use does not have a significant effect on hypertrophy [0.01, 95% confidence interval (CI) [- 0.11, 0.13], t = 0.14, p = 0.90), power (- 0.04, 95% CI [- 0.93, 0.84], t = - 0.29, p = 0.80) or strength (0.10, 95% CI [- 0.08, 0.28], t = 1.48, p = 0.20).
DISCUSSION
Based on the present analysis, there is no evidence-based rationale to advocate for or against the use of OCPs in females partaking in resistance exercise training to increase hypertrophy, power and/or strength. Rather, an individualised approach considering an individual's response to OCPs, their reasons for use and menstrual cycle history may be more appropriate.
REGISTRATION
The review protocol was registered on PROSPERO (ID number and hyperlink: CRD42022365677).
Topics: Female; Humans; Contraceptives, Oral; Gonadal Steroid Hormones; Hypertrophy; Muscle Strength; Muscle, Skeletal; Resistance Training
PubMed: 37755666
DOI: 10.1007/s40279-023-01911-3 -
The Journal of Clinical Endocrinology... Jan 2024Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women. (Meta-Analysis)
Meta-Analysis
CONTEXT
Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.
OBJECTIVE
As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated.
DATA SOURCES
Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched.
STUDY SELECTION
Women with PCOS included in randomized controlled trials (RCTs).
DATA EXTRACTION
We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.
DATA SYNTHESIS
The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/L; 95% CI -174.46, -62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (-16.61 nmol/L; 95% CI -28.51, -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/L; 95% CI -40.65, -13.59) and triglycerides (-0.15 mmol/L; 95% CI -0.29, -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment.
CONCLUSIONS
The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).
Topics: Female; Humans; Metformin; Polycystic Ovary Syndrome; Contraceptives, Oral, Combined; Hypoglycemic Agents; Testosterone; Insulins
PubMed: 37554096
DOI: 10.1210/clinem/dgad465 -
The Cochrane Database of Systematic... Aug 2020Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin.
OBJECTIVES
To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS.
SEARCH METHODS
In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately.
MAIN RESULTS
This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events.
AUTHORS' CONCLUSIONS
In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m and BMI > 30kg/m. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.
Topics: Acne Vulgaris; Adolescent; Adult; Body Mass Index; Cardiovascular Diseases; Contraceptives, Oral, Combined; Drug Therapy, Combination; Endometrial Neoplasms; Female; Hirsutism; Humans; Hypoglycemic Agents; Menstruation Disturbances; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32794179
DOI: 10.1002/14651858.CD005552.pub3