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Fertility and Sterility Dec 2021To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women undergoing FET.
INTERVENTION(S)
We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET.
MAIN OUTCOME MEASURE(S)
Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate.
RESULT(S)
Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs.
CONCLUSION(S)
Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET.
PROSPERO NUMBER
CRD42019157071.
Topics: Cryopreservation; Embryo Transfer; Female; Humans; Live Birth; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Reproductive Techniques, Assisted; Retrospective Studies
PubMed: 34384594
DOI: 10.1016/j.fertnstert.2021.07.002 -
BJOG : An International Journal of... Jan 2019There is no international consensus on how to manage women with a pregnancy of unknown location (PUL). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no international consensus on how to manage women with a pregnancy of unknown location (PUL).
OBJECTIVES
To present a systematic quantitative review summarising the evidence related to management protocols for PUL.
SEARCH STRATEGY
MEDLINE, COCHRANE and DARE databases were searched from 1 January 1984 to 31 January 2017. The primary outcome was accurate risk prediction of women initially diagnosed with a PUL having an ectopic pregnancy (high risk) as opposed to either a failed PUL or intrauterine pregnancy (low risk).
SELECTION CRITERIA
All studies written in the English language, which were not case reports or series that assessed women classified as having a PUL at initial ultrasound.
DATA COLLECTION AND ANALYSIS
Forty-three studies were included. QUADAS-2 criteria were used to assess the risk of bias. We used a novel, linear mixed-effects model and constructed summary receiver operating characteristic curves for the thresholds of interest.
MAIN RESULTS
There was a high risk of differential verification bias in most studies. Meta-analyses of accuracy were performed on (i) single human chorionic gonadotrophin (hCG) cut-off levels, (ii) hCG ratio (hCG at 48 hours/initial hCG), (iii) single progesterone cut-off levels and (iv) the 'M4 model' (a logistic regression model based on the initial hCG and hCG ratio). For predicting an ectopic pregnancy, the areas under the curves (95% CI) for these four management protocols were as follows: (i) 0.42 (0.00-0.99), (ii) 0.69 (0.57-0.78), (iii) 0.69 (0.54-0.81) and (iv) 0.87 (0.83-0.91), respectively.
CONCLUSIONS
The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of PUL.
TWEETABLE ABSTRACT
Pregnancy of unknown location meta-analysis: M4 model has best test performance to predict ectopic pregnancy.
Topics: Chorionic Gonadotropin; Decision Support Techniques; Female; Humans; Logistic Models; Pregnancy; Pregnancy, Ectopic; Progesterone; ROC Curve; Risk Assessment; Sensitivity and Specificity
PubMed: 30129999
DOI: 10.1111/1471-0528.15442 -
Breast Cancer Research and Treatment Jan 2016This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual... (Meta-Analysis)
Meta-Analysis Review
This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents + breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women's health.
Topics: Breast Neoplasms; Contraceptive Agents, Female; Female; Humans; Levonorgestrel; Odds Ratio; Progestins; Risk
PubMed: 26700034
DOI: 10.1007/s10549-015-3663-1 -
Climacteric : the Journal of the... Apr 2018Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including...
Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including micronized progesterone has increased in recent years. Based on a systematic literature review on the impact of menopausal hormone therapy (MHT) containing micronized progesterone on the mammary gland, an international expert panel's recommendations are as follows: (1) estrogens combined with oral (approved) or vaginal (off-label use) micronized progesterone do not increase breast cancer risk for up to 5 years of treatment duration; (2) there is limited evidence that estrogens combined with oral micronized progesterone applied for more than 5 years are associated with an increased breast cancer risk; and (3) counseling on combined MHT should cover breast cancer risk - regardless of the progestogen chosen. Yet, women should also be counseled on other modifiable and non-modifiable breast cancer risk factors in order to balance the impact of combined MHT on the breast.
Topics: Breast; Breast Neoplasms; Endometrium; Estrogen Replacement Therapy; Female; Humans; Menopause; Progesterone; Progestins; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 29384406
DOI: 10.1080/13697137.2017.1421925 -
Clinical Reviews in Allergy & Immunology Jun 2018Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic... (Review)
Review
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans; Omalizumab; Progestins; Tranexamic Acid; Treatment Outcome
PubMed: 27672078
DOI: 10.1007/s12016-016-8585-0 -
The Cochrane Database of Systematic... Oct 2020A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo fresh embryo transfer (ET) cycles with embryos derived from donated oocytes. In both situations, the endometrium is primed with oestrogen and progestogen in different doses and routes of administration.
OBJECTIVES
To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate (LBR).
SEARCH METHODS
The Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trials registers and abstracts of reproductive societies' meetings were searched in June 2020 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. We analysed all available interventions versus placebo, no treatment, or between each other. The primary review outcome was live birth rate. Secondary outcomes were clinical and multiple pregnancy, miscarriage, cycle cancellation, endometrial thickness and adverse effects.
MAIN RESULTS
Thirty-one RCTs (5426 women) were included. Evidence was moderate to very low-quality: the main limitations were serious risk of bias due to poor reporting of methods, and serious imprecision. Stimulated versus programmed cycle We are uncertain whether a letrozole-stimulated cycle compared to a programmed cycle, for endometrial preparation, improves LBR (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.49 to 3.26; 100 participants; one study; very low-quality evidence). Stimulating with follicle stimulating hormone (FSH), letrozole or clomiphene citrate may improve clinical pregnancy rate (CPR) (OR 1.63, 95% CI 1.12 to 2.38; 656 participants; five studies; I = 11%; low-quality evidence). We are uncertain if they reduce miscarriage rate (MR) (OR 0.79, 95% CI 0.36 to 1.71; 355 participants; three studies; I = 0%; very low-quality evidence). Endometrial thickness (ET) may be reduced with clomiphene citrate (mean difference(MD) -1.04, 95% CI -1.59 to -0.49; 92 participants; one study; low-quality evidence). Other outcomes were not reported. Natural versus programmed cycle We are uncertain of the effect from a natural versus programmed cycle for LBR (OR 0.97, 95% CI 0.74 to 1.28; 1285 participants; four studies; I = 0%; very low-quality evidence) and CPR (OR 0.79, 95% CI 0.62 to 1.01; 1249 participants; five studies; I = 60%; very low-quality evidence), while a natural cycle probably reduces the cycle cancellation rate (CCR) (OR 0.60, 95% CI 0.44 to 0.82; 734 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and ET. No study reported other outcomes. Transdermal versus oral oestrogens From low-quality evidence we are uncertain of the effect transdermal compared to oral oestrogens has on CPR (OR 0.86, 95% CI 0.59 to 1.25; 504 participants; three studies; I = 58%) or MR (OR 0.55, 95% CI 0.27 to 1.09; 414 participants; two studies; I = 0%). Other outcomes were not reported. Day of starting administration of progestogen When doing a fresh ET using donated oocytes in a synchronised cycle starting progestogen on the day of oocyte pick-up (OPU) or the day after OPU, in comparison with recipients that start progestogen the day prior to OPU, probably increases the CPR (OR 1.87, 95% CI 1.13 to 3.08; 282 participants; one study, moderate-quality evidence). We are uncertain of the effect on multiple pregnancy rate (MPR) or MR. It probably reduces the CCR (OR 0.28, 95% CI 0.11 to 0.74; 282 participants; one study; moderate-quality evidence). No study reported other outcomes. Gonadotropin-releasing hormone (GnRH) agonist versus control A cycle with GnRH agonist compared to without may improve LBR (OR 2.62, 95% CI 1.19 to 5.78; 234 participants; one study; low-quality evidence). From low-quality evidence we are uncertain of the effect on CPR (OR 1.08, 95% CI 0.82 to 1.43; 1289 participants; eight studies; I = 20%), MR (OR 0.85, 95% CI 0.36 to 2.00; 828 participants; four studies; I = 0%), CCR (OR 0.49, 95% CI 0.21 to 1.17; 530 participants; two studies; I = 0%) and ET (MD -0.08, 95% CI -0.33 to 0.16; 697 participants; four studies; I = 4%). No study reported other outcomes. Among different GnRH agonists From very low-quality evidence we are uncertain if cycles among different GnRH agonists improves CPR or MR. No study reported other outcomes. GnRH agonists versus GnRH antagonists GnRH antagonists compared to agonists probably improves CPR (OR 0.62, 95% CI 0.42 to 0.90; 473 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and MPR. No study reported other outcomes. Aspirin versus control From very low-quality evidence we are uncertain whether a cycle with aspirin versus without improves LBR, CPR, or ET. Steroids versus control From very low-quality evidence we are uncertain whether a cycle with steroids compared to without improves LBR, CPR or MR. No study reported other outcomes.
AUTHORS' CONCLUSIONS
There is insufficient evidence on the use of any particular intervention for endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. In frozen embryo transfers, low-quality evidence showed that clinical pregnancy rates may be improved in a stimulated cycle compared to a programmed one, and we are uncertain of the effect when comparing a programmed cycle to a natural cycle. Cycle cancellation rates are probably reduced in a natural cycle. Although administering a GnRH agonist, compared to without, may improve live birth rates, clinical pregnancy rates will probably be improved in a GnRH antagonist cycle over an agonist cycle. In fresh synchronised oocyte donor cycles, the clinical pregnancy rate is probably improved and cycle cancellation rates are probably reduced when starting progestogen the day of or day after donor oocyte retrieval. Adequately powered studies are needed to evaluate each treatment more accurately.
Topics: Abortion, Spontaneous; Bias; Clomiphene; Cryopreservation; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Embryo, Mammalian; Endometrium; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Letrozole; Live Birth; Oocyte Donation; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Randomized Controlled Trials as Topic
PubMed: 33112418
DOI: 10.1002/14651858.CD006359.pub3 -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
The Cochrane Database of Systematic... Feb 2023The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective...
BACKGROUND
The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective form of EC, and is more effective than other existing oral regimens also used for EC. The Cu-IUD provides the unique benefit of providing ongoing contraception after it is inserted for EC; however, uptake of this intervention has been limited. Progestin IUDs are a popular method of long-acting, reversible contraception. If these devices were also found to be effective for EC, they would provide a critical additional option for women. These IUDs could not only provide EC and ongoing contraception, but additional non-contraceptive benefits, including a reduction in menstrual bleeding, cancer prevention, and pain management.
OBJECTIVES
To examine the safety and effectiveness of progestin-containing IUDs for emergency contraception, compared with copper-containing IUDs, or compared with dedicated oral hormonal methods.
SEARCH METHODS
We considered all randomized controlled trials and non-randomized studies of interventions that compared outcomes for individuals seeking a levonorgestrel IUD (LNG-IUD) for EC to a Cu-IUD or dedicated oral EC method. We considered full-text studies, conference abstracts, and unpublished data. We considered studies irrespective of their publication status and language of publication.
SELECTION CRITERIA
We included studies comparing progestin IUDs with copper-containing IUDs, or oral EC methods for emergency contraception.
DATA COLLECTION AND ANALYSIS
We systematically searched nine medical databases, two trials registries, and one gray literature site. We downloaded all titles and abstracts retrieved by electronic searching to a reference management database, and removed duplicates. Three review authors independently screened titles, abstracts, and full-text reports to determine studies eligible for inclusion. We followed standard Cochrane methodology to assess risk of bias, and analyze and interpret the data. We used GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
We included only one relevant study (711 women); a randomized, controlled, non-inferiority trial comparing LNG-IUDs to Cu-IUDs for EC, with a one-month follow-up. With one study, the evidence was very uncertain for the difference in pregnancy rates, failed insertion rates, expulsion rates, removal rates and the difference in the acceptability of the IUDs. There was also uncertain evidence suggesting the Cu-IUD may slightly increase rates of cramping and the LNG-IUD may slightly increase bleeding and spotting days. AUTHORS' CONCLUSIONS: This review is limited in its ability to provide definitive evidence regarding the LNG-IUD's equivalence, superiority, or inferiority to the Cu-IUD for EC. Only one study was identified in the review, which had possible risks of bias related to randomization and rare outcomes. Additional studies are needed to provide definitive evidence related to the effectiveness of the LNG-IUD for EC.
Topics: Female; Humans; Pregnancy; Contraception, Postcoital; Copper; Intrauterine Devices; Intrauterine Devices, Copper; Progestins; Randomized Controlled Trials as Topic; Steroids
PubMed: 36847591
DOI: 10.1002/14651858.CD013744.pub2 -
The Cochrane Database of Systematic... Jun 2023Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment... (Review)
Review
BACKGROUND
Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is medical therapy with gonadotrophin-releasing hormone analogues (GnRHas) to reduce pain due to endometriosis. One of the adverse effects of GnRHas is a decreased bone mineral density. In addition to assessing the effect on pain, quality of life, most troublesome symptom and patients' satisfaction, the current review also evaluated the effect on bone mineral density and risk of adverse effects in women with endometriosis who use GnRHas versus other treatment options.
OBJECTIVES
To assess the effectiveness and safety of GnRH analogues (GnRHas) in the treatment of painful symptoms associated with endometriosis and to determine the effects of GnRHas on bone mineral density of women with endometriosis.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and the trial registries in May 2022 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) which compared GnRHas with other hormonal treatment options, including analgesics, danazol, intra-uterine progestogens, oral or injectable progestogens, gestrinone and also GnRHas compared with no treatment or placebo. Trials comparing GnRHas versus GnRHas in conjunction with add-back therapy (hormonal or non-hormonal) or calcium-regulation agents were also included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodology as recommended by Cochrane. Primary outcomes are relief of overall pain and the objective measurement of bone mineral density. Secondary outcomes include adverse effects, quality of life, improvement in the most troublesome symptoms and patient satisfaction. Due to high risk of bias associated with some of the studies, primary analyses of all review outcomes were restricted to studies at low risk of selection bias. Sensitivity analysis including all studies was then performed.
MAIN RESULTS
Seventy-two studies involving 7355 patients were included. The evidence was very low to low quality: the main limitations of all studies were serious risk of bias due to poor reporting of study methods, and serious imprecision. Trials comparing GnRHas versus no treatment We did not identify any studies. Trials comparing GnRHas versus placebo There may be a decrease in overall pain, reported as pelvic pain scores (RR 2.14; 95% CI 1.41 to 3.24, 1 RCT, n = 87, low-certainty evidence), dysmenorrhoea scores (RR 2.25; 95% CI 1.59 to 3.16, 1 RCT, n = 85, low-certainty evidence), dyspareunia scores (RR 2.21; 95% CI 1.39 to 3.54, 1 RCT, n = 59, low-certainty evidence), and pelvic tenderness scores (RR 2.28; 95% CI 1.48 to 3.50, 1 RCT, n = 85, low-certainty evidence) after three months of treatment. We are uncertain of the effect for pelvic induration, based on the results found after three months of treatment (RR 1.07; 95% CI 0.64 to 1.79, 1 RCT, n = 81, low-certainty evidence). Besides, treatment with GnRHas may be associated with a greater incidence of hot flushes at three months of treatment (RR 3.08; 95% CI 1.89 to 5.01, 1 RCT, n = 100, low-certainty evidence). Trials comparing GnRHas versus danazol For overall pain, for women treated with either GnRHas or danazol, a subdivision was made between pelvic tenderness, partly resolved and completely resolved. We are uncertain about the effect on relief of overall pain, when a subdivision was made for overall pain (MD -0.30; 95% CI -1.66 to 1.06, 1 RCT, n = 41, very low-certainty evidence), pelvic pain (MD 0.20; 95% CI -0.26 to 0.66, 1 RCT, n = 41, very low-certainty evidence), dysmenorrhoea (MD 0.10; 95% CI -0.49 to 0.69, 1 RCT, n = 41, very low-certainty evidence), dyspareunia (MD -0.20; 95% CI -0.77 to 0.37, 1 RCT, n = 41, very low-certainty evidence), pelvic induration (MD -0.10; 95% CI -0.59 to 0.39, 1 RCT, n = 41, very low-certainty evidence), and pelvic tenderness (MD -0.20; 95% CI -0.78 to 0.38, 1 RCT, n = 41, very low-certainty evidence) after three months of treatment. For pelvic pain (MD 0.50; 95% CI 0.10 to 0.90, 1 RCT, n = 41, very low-certainty evidence) and pelvic induration (MD 0.70; 95% CI 0.21 to 1.19, 1 RCT, n = 41, very low-certainty evidence), the complaints may decrease slightly after treatment with GnRHas, compared to danazol, for six months of treatment. Trials comparing GnRHas versus analgesics We did not identify any studies. Trials comparing GnRHas versus intra-uterine progestogens We did not identify any low risk of bias studies. Trials comparing GnRHas versus GnRHas in conjunction with calcium-regulating agents There may be a slight decrease in bone mineral density (BMD) after 12 months treatment with GnRHas, compared to GnRHas in conjunction with calcium-regulating agents for anterior-posterior spine (MD -7.00; 95% CI -7.53 to -6.47, 1 RCT, n = 41, very low-certainty evidence) and lateral spine (MD -12.40; 95% CI -13.31 to -11.49, 1 RCT, n = 41, very low-certainty evidence). AUTHORS' CONCLUSIONS: For relief of overall pain, there may be a slight decrease in favour of treatment with GnRHas compared to placebo or oral or injectable progestogens. We are uncertain about the effect when comparing GnRHas with danazol, intra-uterine progestogens or gestrinone. For BMD, there may be a slight decrease when women are treated with GnRHas, compared to gestrinone. There was a bigger decrease of BMD in favour of GnRHas, compared to GnRHas in conjunction with calcium-regulating agents. However, there may be a slight increase in adverse effects when women are treated with GnRHas, compared to placebo or gestrinone. Due to a very low to low certainty of the evidence, a wide range of outcome measures and a wide range of outcome measurement instruments, the results should be interpreted with caution.
Topics: Female; Humans; Endometriosis; Danazol; Progestins; Gestrinone; Dysmenorrhea; Calcium; Dyspareunia; Pelvic Pain; Calcium, Dietary; Drug-Related Side Effects and Adverse Reactions; Gonadotropin-Releasing Hormone
PubMed: 37341141
DOI: 10.1002/14651858.CD014788.pub2 -
The Cochrane Database of Systematic... Jun 2023Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC),... (Review)
Review
BACKGROUND
Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC), which provide both progestin and oestrogen, have been examined for their ability to relieve premenstrual symptoms. A combined oral contraceptive containing drospirenone and a low oestrogen dose has been approved for treating PMDD in women who choose combined oral contraceptives for contraception.
OBJECTIVES
To evaluate the effectiveness and safety of COCs containing drospirenone in women with PMS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group trial register, CENTRAL (now containing output from two trials registers and CINAHL), MEDLINE, Embase, PsycINFO, LILACS, Google Scholar, and Epistemonikos on 29 June 2022. We checked included studies' reference lists and contacted study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCT) that compared COCs containing drospirenone with placebo or with another COC for treatment of women with PMS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were effects on premenstrual symptoms that were prospectively recorded, and withdrawal due to adverse events. Secondary outcomes included effects on mood, adverse events, and response rate to study medications.
MAIN RESULTS
We included five RCTs (858 women analysed, most diagnosed with PMDD). The evidence was very low to moderate quality; the main limitations were serious risk of bias due to poor reporting of study methods, and serious inconsistency and imprecision. COCs containing drospirenone and ethinylestradiol (EE) versus placebo COCs containing drospirenone and EE may improve overall premenstrual symptoms (standardised mean difference (SMD) -0.41, 95% confidence interval (CI) -0.59 to -0.24; 2 RCTs, N = 514; I = 64%; low-quality evidence); and functional impairment due to premenstrual symptoms in terms of productivity (mean difference (MD) -0.31, 95% CI -0.55 to -0.08; 2 RCTs, N = 432; I = 47%; low-quality evidence), social activities (MD -0.29, 95% CI -0.54 to -0.04; 2 RCTs, N = 432; I = 53%; low-quality evidence), and relationships (MD -0.30, 95% CI -0.54 to -0.06; 2 RCTs, N = 432; I = 45%; low-quality evidence). The effects from COCs containing drospirenone may be small to moderate. COCs containing drospirenone and EE may increase withdrawal from trials due to adverse effects (odds ratio (OR) 3.41, 95% CI 2.01 to 5.78; 4 RCT, N = 776; I = 0%; low-quality evidence). This suggests that if you assume the risk of withdrawal due to adverse effects from placebo is 3%, the risk from drospirenone plus EE will be between 6% and 16%. We are uncertain of the effect of drospirenone plus EE on premenstrual mood symptoms, when measured by validated tools that were not developed to assess premenstrual symptoms. COCs containing drospirenone may lead to more adverse effects in total (OR 2.31, 95% CI 1.71 to 3.11; 3 RCT, N = 739; I = 0%; low-quality evidence). This suggests that if you assume the risk of having adverse effects from placebo is 28%, the risk from drospirenone plus EE will be between 40% and 54%. It probably leads to more breast pain, and may lead to more nausea, intermenstrual bleeding, and menstrual disorder. Its effect on nervousness, headache, asthenia, and pain is uncertain. There was no report of any rare but serious adverse effects, such as venous thromboembolism in any of the included studies. COCs containing drospirenone may improve response rate (OR 1.65, 95% CI 1.13 to 2.40; 1 RCT, N = 449; I not applicable; low-quality evidence). This suggests that if you assume the response rate from placebo is 36%, the risk from drospirenone plus EE will be between 39% and 58%. We did not identify any studies that compared COCs containing drospirenone with other COCs.
AUTHORS' CONCLUSIONS
COCs containing drospirenone and EE may improve premenstrual symptoms that result in functional impairments in women with PMDD. The placebo also had a significant effect. COCs containing drospirenone and EE may lead to more adverse effects compared to placebo. We do not know whether it works after three cycles, helps women with less severe symptoms, or is better than other combined oral contraceptives that contain a different progestogen.
Topics: Female; Humans; Contraceptives, Oral, Combined; Drug-Related Side Effects and Adverse Reactions; Estrogens; Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Progestins
PubMed: 37365881
DOI: 10.1002/14651858.CD006586.pub5