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The Cochrane Database of Systematic... Jan 2005Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs).
OBJECTIVES
To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched.
SELECTION CRITERIA
RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included.
DATA COLLECTION AND ANALYSIS
Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects.
MAIN RESULTS
Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4).
AUTHORS' CONCLUSIONS
This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.
Topics: Anovulation; Contraceptives, Oral, Combined; Estrogen Antagonists; Female; Humans; Infertility, Female; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 15674894
DOI: 10.1002/14651858.CD002249.pub3 -
Current Opinion in Obstetrics &... Dec 2004Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations... (Review)
Review
PURPOSE OF REVIEW
Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations it should be used. This review examines the recent literature in order to ascertain the evidence for the benefits and disadvantages of using metformin in women with polycystic ovary syndrome.
RECENT FINDINGS
A Cochrane systematic review and metaanalysis examined the evidence for metformin in treating polycystic ovary syndrome. Since this was published there have been a number of new trials, some of which have been reasonably large involving participants from many different countries.
SUMMARY
Evidence shows that metformin is effective in inducing ovulation, has some marginal benefit in improving aspects of the metabolic syndrome, improves objective measures of hirsutism, and seems to be effective in both obese and lean individuals. However, it has significant side effects, and the high levels of effectiveness that were reported by some early trials have not been replicated. Metformin should always be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.
Topics: Anovulation; Body Weight; Clomiphene; Drug Therapy, Combination; Female; Fertility Agents, Female; Glucose Metabolism Disorders; Gonadotropins; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome
PubMed: 15534444
DOI: 10.1097/00001703-200412000-00008 -
The Cochrane Database of Systematic... Jan 2014Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, as a surrogate for the hormonal surge seen in spontaneous menstrual cycles, to control the timing of ovulation and the timing of sexual intercourse. Ovulation triggers given without reliable evidence of oocyte maturity could be inappropriately timed; they increase costs, and the need to time intercourse precisely after the ovulation trigger is given adds to psychological stress.This is an update of a Cochrane review first published in Issue 3, 2008, of the Cochrane Database of Systematic Reviews.
OBJECTIVES
To determine the benefits and harms of administering an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents in comparison with spontaneous ovulation following ovulation induction.
SEARCH METHODS
We updated searches of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to November 2013. We checked conference proceedings, trial registries and reference lists and contacted researchers.
SELECTION CRITERIA
Parallel-group, randomised, controlled trials (RCTs) evaluating the administration of an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents.
DATA COLLECTION AND ANALYSIS
We independently assessed trial eligibility and trial quality and extracted data. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and used the random-effects model in meta-analyses when significant heterogeneity was present. We assessed overall quality of the evidence by using the GRADE approach.
MAIN RESULTS
No new trials were identified. This review includes two RCTs with low risk of bias that compared urinary human chorionic gonadotrophin (hCG) versus no treatment in anovulatory women receiving clomiphene citrate. Urinary hCG did not result in an increase in live birth rate over no hCG (OR 0.97, 95% CI 0.52 to 1.83; two trials, 305 participants, I(2) = 16%; low-quality evidence), but very serious imprecision around the effect estimate reduces our confidence in the apparent lack of effect of hCG as an ovulation trigger in clomiphene-induced cycles in anovulatory women.Among this review's secondary outcomes, urinary hCG may not increase ovulation rate (OR 0.99, 95% CI 0.36 to 2.77; two trials, 305 participants, I(2) = 55%; low-quality evidence), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.89; two trials, 305 participants, I(2) = 35%; low-quality evidence) or miscarriage rate in pregnant women (OR 1.19, 95% CI 0.17 to 8.23; two trials, 54 participants, I(2) = 0%; low-quality evidence). Multiple pregnancies and preterm deliveries were uncommon, and ovarian hyperstimulation syndrome, adverse events and deaths were not reported as outcomes in either trial. We found no trials evaluating other ovulation triggers.
AUTHORS' CONCLUSIONS
Evidence is inadequate to recommend or refute the use of urinary hCG as an ovulation trigger in anovulatory women treated with clomiphene citrate. We found no trials evaluating the use of ovulation triggers in anovulatory women treated with other ovulation-inducing agents.
Topics: Anovulation; Chorionic Gonadotropin; Clomiphene; Female; Fertility Agents, Female; Humans; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Control Agents
PubMed: 24482059
DOI: 10.1002/14651858.CD006900.pub3 -
The Cochrane Database of Systematic... Jul 2009Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.
OBJECTIVES
To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008 ), the Cochrane Central Register of Controlled Trials (Cochrane Library, September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008).
SELECTION CRITERIA
Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent.
DATA COLLECTION AND ANALYSIS
Thirty nine trials (3576 subjects) were included for analysis, 31 of them using metformin and involving 2625 participants.
MAIN RESULTS
Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 2.21(CI 1.57 to 3.10) for metformin versus placebo and 3.93(CI 2.32 to 6.65) for metformin and clomiphene versus clomiphene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomiphene (OR 1.58, CI 1.20 to 2.07). Nevertheless, these benefits were not translated into live birth rates.Metformin has a significant effect in reducing fasting insulin levels (WMD -4.20 mIU/L, CI -7.68 to -0.73); however, the reduction was only significant in the non-obese group (BMI < 30 kg/m2). Treatment effect on serum testosterone concentration was observed; but the magnitude of the reduction was greater in the non-obese group compared with the obese group (WMD -1.79 versus. -0.30 nmol/L). Metformin has no effect on serum lipid profiles. Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported.
AUTHORS' CONCLUSIONS
In agreement with the previous review, metformin is still of benefit in improving ovulation and pregnancy rates. However, metformin does not improve live birth whether it is used alone or in combination with clomiphene. In addition, metformin has limited effect on metabolic parameters, especially in obese women with PCOS. Therefore, the use of metformin in improvement of reproductive outcomes or in reducing the risk of developing metabolic syndrome in women with PCOS appears to be limited.
Topics: Anovulation; Chromans; Female; Humans; Hypoglycemic Agents; Inositol; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Thiazoles; Thiazolidinediones
PubMed: 19588338
DOI: 10.1002/14651858.CD003053.pub2 -
Hormones (Athens, Greece) Sep 2021Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line pharmacological treatment for women with WHO Group II anovulation or PCOS. However, the use of letrozole as an ovulation induction agent is not FDA or EMA approved, and its use is "off-label." The main concern with respect to letrozole regards its potential teratogenic effect on the fetus.
PURPOSE
To determine whether the probability of ovulation is higher with letrozole as compared to clomiphene citrate (CC) in anovulatory women with PCOS.
METHODS
Randomized controlled trials (RCTs) comparing letrozole versus CC used for ovulation induction in infertile women with PCOS followed by timed intercourse (TI) or intrauterine insemination (IUI) were included in this meta-analysis. Primary outcome was ovulation. Secondary outcomes were live birth, clinical pregnancy, miscarriage, multiple pregnancy, and congenital anomalies. Subgroup analysis included patients who received letrozole or CC as first-line treatment, and patients with PCOS diagnosed according to the Rotterdam criteria.
RESULTS
Twenty-six RCTs published between 2006 and 2019, involving 4168 patients who underwent 8310 cycles of ovulation induction, were included. The probability of ovulation was significantly higher in letrozole as compared to CC cycles (RR: 1.148, 95% CI: 1.077 to 1.223, 3017 women, 19 trials, I: 47.7%, low-quality evidence).
CONCLUSION
A higher probability of ovulation is expected in infertile patients with PCOS treated with letrozole as compared to CC. The higher ovulation rate might have contributed to the higher clinical pregnancy and live birth rate. This finding is also true for patients who were administered letrozole as first-line treatment.
TRIAL REGISTRATION
CRD42019125166.
Topics: Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy
PubMed: 34033068
DOI: 10.1007/s42000-021-00289-z -
The European Journal of Contraception &... Jun 2017Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated... (Review)
Review
INTRODUCTION
Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated with significant quality of life and psychological impairment. Women with abnormalities in androgen metabolism may have accompanying anovulation and/or polycystic ovary syndrome (PCOS), both of which have reproductive and metabolic implications if left untreated. Cyproterone acetate (CPA), combined with ethinylestradiol (EE), is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age.
OBJECTIVE
To review the data on the efficacy and safety of CPA 2 mg/EE 35 μg for the treatment of hyperandrogenic skin symptoms in women.
METHODS
A non-systematic narrative review based on a literature search of the PubMed database.
RESULTS
Seventy-eight studies were identified. The majority of sufficiently powered studies show a high efficacy of CPA 2 mg/EE 35 μg in the treatment of severe acne and hirsutism. Studies show that therapeutic response in women with hirsutism requires a long-term approach and that hyperandrogenic skin symptoms in patients with PCOS are efficiently treated. Additional benefits include cycle control and, in some women, improvement in mood and perception of body image. Safety and tolerability data are summarized by the pharmacovigilance risk assessment committee (PRAC) of the European Medicine's Agency's (EMA).
CONCLUSIONS
This review provides a comprehensive overview about the efficacy of CPA 2 mg/EE 35 μg in the treatment of hyperandrogenic skin symptoms, thus allowing both health care professionals and women to balance the risks and benefits of treatment based on evidence.
Topics: Acne Vulgaris; Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Skin Diseases; Treatment Outcome
PubMed: 28447864
DOI: 10.1080/13625187.2017.1317339 -
The Cochrane Database of Systematic... 2000Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection... (Review)
Review
BACKGROUND
Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned of the risk of post-surgical adhesion formation. It was replaced by medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Although effective, it is an expensive, stressful and time consuming form of treatment requiring intensive monitoring. A new surgical therapy, laparoscopic ovarian "drilling", may avoid or reduce the need, or facilitate the use, of gonadotrophins for inducing ovulation. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. It has been claimed in many uncontrolled observational studies that it is followed, at least temporarily, by a high rate of spontaneous postoperative ovulation and conception, or that subsequent medical ovulation induction becomes easier.
OBJECTIVES
To determine the effectiveness of laparoscopic ovarian drilling for ovulation induction in subfertile women with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS).
SEARCH STRATEGY
The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTS). A computerised MEDLINE search was used to identify non randomised controlled trials.
SELECTION CRITERIA
Trials were eligible for inclusion if treatment consisted of laparoscopic ovarian drilling in order to induce ovulation in subfertile women with PCOS and compared with a concurrent control group.
DATA COLLECTION AND ANALYSIS
Fourteen trials were identified; eight were included in the review of which seven were randomised. All trials were assessed for quality criteria. The main studied outcomes were ovulation and pregnancy rates. Miscarriage rate, multiple pregnancy rate, and incidence of overstimulation and ovarian hyperstimulation syndrome rate were secondary outcomes.
MAIN RESULTS
With the exception of multiple pregnancy rates no differences were demonstrated for any of the interventions studied but the numbers of patients who have been randomised to controlled studies at this time is insufficient to conclude that laparoscopic ovarian drilling is more effective than gonadotrophin therapy for other outcomes.
REVIEWER'S CONCLUSIONS
The value of laparoscopic ovarian drilling as a primary treatment for subfertile patients with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS) is undetermined. There is insufficient evidence to determine a difference in ovulation or pregnancy rates when compared to gonadotrophin therapy as a secondary treatment for clomiphene resistant women. Multiple pregnancy rates are reduced in those women who conceive following laparoscopic drilling. None of the studied modalities of drilling technique had any obvious advantages.
Topics: Anovulation; Diathermy; Female; Humans; Infertility, Female; Laparoscopy; Laser Therapy; Ovulation Induction; Polycystic Ovary Syndrome
PubMed: 10796746
DOI: 10.1002/14651858.CD001122 -
The Journal of Clinical Endocrinology... Mar 2006For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to... (Review)
Review
CONTEXT
For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction.
EVIDENCE ACQUISITION
We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine.
EVIDENCE SYNTHESIS
Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders.
CONCLUSIONS
Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.
Topics: Anovulation; Aromatase Inhibitors; Clomiphene; Female; Humans; Ovulation; Ovulation Induction
PubMed: 16384846
DOI: 10.1210/jc.2005-1923 -
Gynecological Endocrinology : the... Aug 2021To study the association between hyperandrogenism (HA) and adverse pregnancy outcomes in patients with different polycystic ovary syndrome phenotypes undergoing... (Meta-Analysis)
Meta-Analysis
Association between hyperandrogenism and adverse pregnancy outcomes in patients with different polycystic ovary syndrome phenotypes undergoing fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.
OBJECTIVE
To study the association between hyperandrogenism (HA) and adverse pregnancy outcomes in patients with different polycystic ovary syndrome phenotypes undergoing fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
METHODS
We reviewed all eligible articles published up to October 2020 after searching in PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, and CNKI databases. The primary outcomes were the clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR), whereas the secondary outcomes were the number of retrieved oocytes and endometrial thickness. Risk ratios (RRs) or mean differences with 95% confidence intervals (CIs) were calculated to estimate the HA impact on IVF/ICSI outcomes in patients with polycystic ovary syndrome (PCOS) phenotypes.
RESULTS
Of the 789 trials identified, nine retrospective studies involving 3037 patients with PCOS were included. Compared to the PCOS group with normal androgen levels, the PCOS group with HA exhibited increased MR (RR: 1.56, 95% CI: 1.13, 2.16); the CPR (RR: 0.88, 95% CI: 0.77, 1.01) and LBR (RR: 0.79, 95% CI: 0.55, 1.11) were not significantly different between these groups. Subgroup analysis revealed that the CPR was lower in the polycystic ovarian (PCO)-morphology + HA + oligo-anovulation (AO) group than in the PCO + AO group (RR: 0.81, 95% CI: 0.67, 0.99). Among Asians, the PCOS/HA group had increased MR (RR: 1.56, 95% CI: 1.06, 2.31) and showed thinner endometrial thickness. However, among Caucasians, no differences were observed between the two groups.
CONCLUSIONS
HA may have adverse effects on clinical pregnancy and miscarriage outcomes in different PCOS phenotypes, particularly among Asians.
Topics: Abortion, Spontaneous; Asian People; Endometrium; Female; Humans; Hyperandrogenism; Live Birth; Oocyte Retrieval; Phenotype; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 33703999
DOI: 10.1080/09513590.2021.1897096 -
The Cochrane Database of Systematic... Sep 2012Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with anovulation. Irregular bleeding due to... (Review)
Review
BACKGROUND
Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with anovulation. Irregular bleeding due to oligo/anovulation (previously called dysfunctional uterine bleeding or DUB) is more common at the extremes of reproductive life, and in women with ovulatory disorders such as polycystic ovary syndrome (PCOS). In anovulatory cycles there may be prolonged oestrogen stimulation of the endometrium without progesterone withdrawal and so cycles are irregular and bleeding may be heavy. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination, are widely used in the management of irregular menstrual bleeding, but the regime, dose and type of progestogen used vary widely, with little consensus about the optimum treatment approach.
OBJECTIVES
To determine the effectiveness and acceptability of progestogens alone or in combination with oestrogens in the regulation of irregular menstrual bleeding associated with oligo/anovulation.
SEARCH METHODS
We searched the following databases in February 2012: Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and reference lists of articles.
SELECTION CRITERIA
All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular menstrual bleeding associated with oligo/anovulation.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two review authors. All authors were experts in the content of this review.
MAIN RESULTS
No randomised trials were identified that compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with oligo/anovulation.
AUTHORS' CONCLUSIONS
There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular menstrual bleeding associated with anovulation. There is no consensus about which regimens are most effective. Further research is needed to establish the role of these hormonal treatments in the management of this common gynaecological problem.
Topics: Adult; Anovulation; Drug Therapy, Combination; Estrogens; Female; Humans; Menorrhagia; Progestins
PubMed: 22972055
DOI: 10.1002/14651858.CD001895.pub3