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BMJ Sexual & Reproductive Health Jan 2020To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women.
OBJECTIVES
To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women.
METHODS
We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings.
RESULTS
From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users.
CONCLUSION
The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.
Topics: Adolescent; Adult; Contraception Behavior; Female; HIV Infections; Humans; Incidence; Intrauterine Devices, Copper
PubMed: 31919240
DOI: 10.1136/bmjsrh-2019-200512 -
BMJ Sexual & Reproductive Health Jan 2020To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
OBJECTIVE
To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
METHODS
We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.
RESULTS
In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.
CONCLUSIONS
High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.
Topics: Adolescent; Adult; Female; HIV Infections; Hormonal Contraception; Humans
PubMed: 31919239
DOI: 10.1136/bmjsrh-2019-200509 -
The Cochrane Database of Systematic... Oct 2019Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the... (Review)
Review
BACKGROUND
Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.Catamenial epilepsy and seizure exacerbation is common in women with epilepsy, and may have a significant negative impact on quality of life. Women may not be receiving appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases to 10 January 2019: Cochrane Register of Studies (CRS Web; includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE (Ovid: 1946 to 9 January 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials (RCTs) of blinded or opeṉlabel design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. Types of interventions included: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and mean change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
We identified 62 records from the databases and search strategies. Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for mean change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results on the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported that the decrease in seizure frequency from baseline in the progesterone group was significantly higher than the decrease in seizure frequency from baseline in the placebo group.Results of secondary efficacy outcomes showed no significant difference in terms of treatment withdrawal for any reason in the pooled progesterone RCTs when compared to placebo (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or for treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals from the norethisterone RCTs were reported. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.We judged the evidence from the included progesterone RCTs to be of low to moderate certainty due to risk of bias and from the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.Our review highlighted an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those patients who do not have regular menses. Further clinical trials are needed in this area.
PubMed: 31608992
DOI: 10.1002/14651858.CD013225.pub2 -
The Cochrane Database of Systematic... Aug 2019Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their...
BACKGROUND
Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their physical, emotional, social and material quality of life. Whilst abnormal menstrual bleeding may be associated with underlying pathology, in the present context, HMB is defined as excessive menstrual bleeding in the absence of other systemic or gynaecological disease. The first-line therapy is usually medical, avoiding possibly unnecessary surgery. Of the wide variety of medications used to reduce HMB, oral progestogens were originally the most commonly prescribed agents. This review assesses the effectiveness of two different types and regimens of oral progestogens in reducing ovulatory HMB.This is the update of a Cochrane review last updated in 2007, and originally named "Effectiveness of cyclical progestagen therapy in reducing heavy menstrual bleeding" (1998).
OBJECTIVES
To determine the effectiveness, safety and tolerability of oral progestogen therapy taken either during the luteal phase (short cycle) or for a longer course of 21 days per cycle (long cycle), in achieving a reduction in menstrual blood loss in women of reproductive age with HMB.
SEARCH METHODS
In January 2019 we searched Cochrane Gynaecology and Fertility's specialized register, CENTRAL, MEDLINE, Embase, CINAHL and PsycInfo. We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved trials. We also checked citation lists of review articles to identify trials.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing different treatments for HMB that included cyclical oral progestogens were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trials for risk of bias and extracted data. We contacted trial authors for clarification of methods or additional data when necessary. We only assessed adverse events if they were separately measured in the included trials. We compared cyclical oral progestogen in different regimens and placebo or other treatments. Our primary outcomes were menstrual blood loss and satisfaction with treatment; the secondary outcomes were number of days of bleeding, quality of life, compliance and acceptability of treatment, adverse events and costs.
MAIN RESULTS
This review identified 15 randomized controlled trials (RCTs) with 1071 women in total. Most of the women knew which treatment they were receiving, which may have influenced their judgements about menstrual blood loss and satisfaction. Other aspects of trial quality varied among trials.We did not identify any RCTs comparing progestogen treatment with placebo. We assessed comparisons between oral progestogens and other medical therapies separately according to different regimens.Short-cycle progestogen therapy during the luteal phase (medroxyprogesterone acetate or norethisterone for 7 to 10 days, from day 15 to 19) was inferior to other medical therapy, including tranexamic acid, danazol and the progestogen-releasing intrauterine system (Pg-IUS (off of the market since 2001)), releasing 60 mcg of progesterone daily, with respect to reduction of menstrual blood loss (mean difference (MD) 37.29, 95% confidence interval (CI) 17.67 to 56.91; I = 50%; 6 trials, 145 women). The rate of satisfaction and the quality of life with treatment was similar in both groups. The number of bleeding days was greater on the short cycle progestogen group compared to other medical treatments. Adverse events (such as gastrointestinal symptoms and weight gain) were more likely with danazol when compared with progestogen treatment. We note that danazol is no longer in general use for treating HMB.Long-cycle progestogen therapy (medroxyprogesterone acetate or norethisterone), from day 5 to day 26 of the menstrual cycle, is also inferior to the levonorgestrel-releasing intrauterine system (LNG-IUS), releasing tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss (MD 16.88, 95% CI 10.93 to 22.84; I = 87%; 4 trials, 355 women). A higher proportion of women taking norethisterone found their treatment unacceptable compared to women having Pg-IUS (Peto odds ratio (OR) 0.12, 95% CI 0.03 to 0.40; 1 trial, 40 women). However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the LNG-IUS. No trials reported on days of bleeding or quality of life for this comparison.The evidence supporting these findings was limited by low or very low gradings of quality; thus, we are uncertain about the findings and there is a potential that they may change if we identify other trials.
AUTHORS' CONCLUSIONS
Low- or very low-quality evidence suggests that short-course progestogen was inferior to other medical therapy, including tranexamic acid, danazol and the Pg-IUS with respect to reduction of menstrual blood loss. Long cycle progestogen therapy (medroxyprogesterone acetate or norethisterone) was also inferior to the LNG-IUS, tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss.
Topics: Danazol; Female; Humans; Intrauterine Devices, Medicated; Medroxyprogesterone Acetate; Menorrhagia; Progesterone; Progestins; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 31425626
DOI: 10.1002/14651858.CD001016.pub3 -
Cancer Management and Research 2019This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received...
Weight control is vital for patients with early-stage endometrial cancer or complex atypical hyperplasia who have received progestin therapy to spare fertility: a systematic review and meta-analysis.
This study aimed to identify potential prognostic factors for patients with complex atypical hyperplasia (CAH) or early-stage endometrial cancer (EC) who received progestin therapy to spare fertility and, thus, improve the management of this patient group. The PubMed, PMC, EMBASE, Web of Science, and Cochrane databases were searched for correlational studies published in English. Studies that evaluated the prognosis of patients with CAH or early-stage EC were pooled for a systematic review and meta-analysis. In total, 31 eligible studies, including 8 prospective and 23 retrospective studies involving 1099 patients, were included in this analysis. The most commonly used progestin agents were medroxyprogesterone acetate (MPA, 47.0%) and megestrol acetate (MA, 25.5%). The total complete response (CR) rate was 75.8% (833/1099), and the median time to CR with first-line progestin therapy was 6 months. In total, 294 (26.8%) patients who achieved CR became pregnant spontaneously (28 cases) or through assisted reproductive technology (127 cases). During the median follow-up of 39 months, 245 (22.3%) women developed recurrence. Only one patient (0.09%) died of the disease. The meta-analysis showed that compared to a BMI<25 kg/m and CAH, a body mass index (BMI) ≥25 kg/m (=0.0004, odds ratios (OR), 0.4; 95% confidence interval, 0.3-0.6) and EC (=0.0000, OR, 0.3; 95% confidence interval, 0.2-0.6) were significantly associated with a higher likelihood of a CR. Patients with a BMI≥25 kg/m (=0.0007, OR, 2.5; 95% confidence interval, 1.4-4.3), PCOS (=0.0006, OR, 3.4; 95% confidence interval, 1.5-7.9), and EC (=0.0344, OR, 2.8; 95% confidence interval, 1.4-5.3) had a significantly higher risk of recurrence. In general, patients with CAH or early-stage EC who were treated with progesterone therapy had a favorable prognosis. However, the recurrence risk was not insignificant. Weight control is crucial for improving the clinical management of this patient group.
PubMed: 31190979
DOI: 10.2147/CMAR.S194607 -
BMJ Global Health 2019Depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) may facilitate self-administration and expand contraceptive access. To inform WHO...
INTRODUCTION
Depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) may facilitate self-administration and expand contraceptive access. To inform WHO guidelines on self-care interventions, we conducted a systematic review and meta-analysis comparing self-administration versus provider administration of injectable contraception on outcomes of pregnancy, side effects/adverse events, contraceptive uptake, contraceptive continuation, self-efficacy/empowerment and social harms.
METHODS
We searched PubMed, Cumulative Index to Nursing and Allied Health Literature, LILACS and EMBASE in September 2018 for peer-reviewed studies comparing women who received injectable contraception with the option of self-administration with women who received provider-administered injectable contraception on at least one outcome of interest. Risk of bias was assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for non-randomised studies. Meta-analysis was conducted using random-effects models to generate pooled estimates of relative risk (RR).
RESULTS
Six studies with 3851 total participants met the inclusion criteria: three RCTs and three controlled cohort studies. All studies examined self-injection of DMPA-SC; comparison groups were either provider-administered DMPA-SC or provider-administered intramuscular DMPA. All studies followed women through 12 months of contraceptive coverage and measured (dis)continuation of injectable contraception. Meta-analysis found higher rates of continuation with self-administration compared with provider administration in three RCTs (RR: 1.27, 95% CI 1.16 to 1.39) and three controlled cohort studies (RR: 1.18, 95% CI 1.10 to 1.26). Four studies reported pregnancies; all showed no difference across study arms. Four studies reported side effects/adverse events; while two controlled cohort studies showed increased injection site reactions with self-administration, no other side effects increased with self-administration. One study found no difference in social harms. No studies reported measuring uptake or self-efficacy/empowerment.
CONCLUSION
A growing evidence base suggests that self-administration of DMPA-SC can equal or improve contraceptive continuation rates compared with provider administration. This benefit comes without notable increases in pregnancy or safety concerns. Self-injection of DMPA-SC is a promising approach to increasing contraceptive use.
PubMed: 31179026
DOI: 10.1136/bmjgh-2018-001350 -
The Cochrane Database of Systematic... Apr 2019Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates for shorter-term methods such as oral and injectable contraceptives are much lower. In large part, this disparity reflects difficulties in ongoing adherence to the contraceptive regimen and low continuation rates. Correct use of contraceptives to ensure effectiveness is vital to reducing unintended pregnancy.
OBJECTIVES
To determine the effectiveness of strategies aiming to improve adherence to, and continuation of, shorter-term hormonal methods of contraception compared with usual family planning care.
SEARCH METHODS
We searched to July 2018 in the following databases (without language restrictions): The Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), PubMed via MEDLINE, POPLINE, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing strategies aimed to facilitate adherence and continuation of shorter-term hormonal methods of contraception (such as oral contraceptives (OCs), injectable depot medroxyprogesterone acetate (DMPA or Depo-Provera), intravaginal ring, or transdermal patch) with usual family planning care in reproductive age women seeking to avoid pregnancy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Primary outcomes were continuation or discontinuation of contraceptive method, rates of discontinuation due to adverse events (menstrual disturbances and all other adverse events), and adherence to method use as indicated by missed pills and on-time/late injections. Pregnancy was a secondary outcome.
MAIN RESULTS
We included 10 RCTs involving 6242 women. Six trials provided direct in-person counseling using either multiple counseling contacts or multiple components during one visit. Four trials provided intensive reminders of appointments or next dosing, of which two provided additional educational health information as well as reminders. All trials stated 'usual care' as the comparison.The certainty of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of methodological detail, lack of blinding, and incomplete outcome data), inconsistency, indirectness, and imprecision.Continuation of hormonal contraceptive methodsIt is uncertain whether intensive counseling improves continuation of hormonal contraceptive methods compared with usual care (OR 1.28, 95% CI 1.07 to 1.54; 2624 participants; 6 studies; I = 79%; very low certainty evidence). The evidence suggested: if the chance of continuation with usual care is 39%, the chance of continuation with intensive counseling would be between 41% and 50%. The overall pooled OR suggested continuation of improvement, however, when stratified by contraceptive method type, the positive results were restricted to DMPA.It is uncertain whether reminders (+/- educational information) improve continuation of hormonal contraceptive methods compared with usual care (OR 1.33, 95% CI 1.03 to 1.73; 933 participants; 2 studies; I = 69%; very low certainty evidence).The evidence suggested: if the chance of continuation with usual care is 52%, the chance of continuation with reminders would be between 52% and 65%.Discontinuation due to adverse eventsThe evidence suggested that counseling may be associated with a decreased rate of discontinuation due to adverse events compared with usual care, with a lower rate of discontinuation due to menstrual disturbances (OR 0.20, 95% CI 0.11 to 0.37; 350 participants; 1 study; low certainty evidence), but may make little or no difference to all other adverse events (OR 0.73, 95% CI 0.36 to 1.47; 350 participants; 1 study; low certainty evidence). The evidence suggested: if the chance of discontinuation with usual care due to menstrual disturbances is 32%, the chance of discontinuation with intensive counseling would be between 5% and 15%; and that if the chance of discontinuation with usual care due to other adverse events is 55%, the chance of discontinuation with intensive counseling would be between 30% and 64%.Discontinuation was not reported among trials that investigated the use of reminders (+/- educational information).Adherence Adherence was not reported among trials that investigated the use of intensive counseling.Among trials that investigated reminders (+/- educational information), there was no conclusive evidence of a difference in adherence as indicated by missed pills (MD 0.80, 95% CI -1.22 to 2.82; 73 participants; 1 study; moderate certainty evidence) or by on-time injections (OR 0.84, 95% CI 0.54 to 1.29; 350 participants; 2 studies; I = 0%; low certainty evidence). The evidence suggested: if the chance of adherence to method use as indicated by on-time injections with usual care is 50%, the chance of adherence with method use as indicated by on-time injections with reminders would be between 35% and 56%.PregnancyThere was no conclusive evidence of a difference in rates of pregnancy between intensive counseling and usual care (OR 1.24, 95% CI 0.98 to 1.57; 1985 participants; 3 studies; I = 0%, very low certainty evidence). The evidence suggested: if the chance of pregnancy with usual care is 18%, the chance of pregnancy with counseling would be between 18% and 25%.Pregnancy was not reported among trials that investigated the use of reminders (+/- educational information).
AUTHORS' CONCLUSIONS
Despite the importance of this topic, studies have not been published since the last review in 2013 (nine studies) with only one study added in 2019 that neither changed the results nor improved the certainty of evidence.Overall, the certainty of evidence for strategies to improve adherence and continuation of contraceptives is low. Intensive counseling and reminders (with or without educational information) may be associated with improved continuation of shorter-term hormonal contraceptive methods when compared with usual family planning care. However, this should be interpreted with caution due to the low certainty of the evidence. Included trials used a variety of shorter-term hormonal contraceptive methods which may account for the high heterogeneity. It is possible that the effectiveness of strategies for improving adherence and continuation are contingent on the contraceptive method targeted. There was limited reporting of objectively measurable outcomes (e.g. electronic monitoring device) among included studies. Future trials would benefit from standardized definitions and measurements of adherence, and consistent terminology for describing interventions and comparisons. Further research requires larger studies, follow-up of at least one year, and improved reporting of trial methodology.
Topics: Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Counseling; Family Planning Services; Female; Humans; Pregnancy; Pregnancy, Unplanned
PubMed: 31013349
DOI: 10.1002/14651858.CD004317.pub5 -
The Cochrane Database of Systematic... Apr 2019High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres...
BACKGROUND
High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE), and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this, the third of a series of three reviews about preventive strategies for HAI, we assessed the effectiveness of miscellaneous and non-pharmacological interventions.
OBJECTIVES
To assess the clinical effectiveness and adverse events of miscellaneous and non-pharmacological interventions for preventing acute HAI in people who are at risk of developing high altitude illness in any setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in January 2019. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials.
SELECTION CRITERIA
We included randomized controlled trials conducted in any setting where non-pharmacological and miscellaneous interventions were employed to prevent acute HAI, including preacclimatization measures and the administration of non-pharmacological supplements. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with, and without, a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant intervention was administered before the beginning of ascent.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures employed by Cochrane.
MAIN RESULTS
We included 20 studies (1406 participants, 21 references) in this review. Thirty studies (14 ongoing, and 16 pending classification (awaiting)) will be considered in future versions of this suite of three reviews as appropriate. We report the results for the primary outcome of this review (risk of AMS) by each group of assessed interventions.Group 1. Preacclimatization and other measures based on pressureUse of simulated altitude or remote ischaemic preconditioning (RIPC) might not improve the risk of AMS on subsequent exposure to altitude, but this effect is uncertain (simulated altitude: risk ratio (RR) 1.18, 95% confidence interval (CI) 0.82 to 1.71; I² = 0%; 3 trials, 140 participants; low-quality evidence. RIPC: RR 3.0, 95% CI 0.69 to 13.12; 1 trial, 40 participants; low-quality evidence). We found evidence of improvement of this risk using positive end-expiratory pressure (PEEP), but this information was derived from a cross-over trial with a limited number of participants (OR 3.67, 95% CI 1.38 to 9.76; 1 trial, 8 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 2. Supplements and vitaminsSupplementation of antioxidants, medroxyprogesterone, iron or Rhodiola crenulata might not improve the risk of AMS on exposure to high altitude, but this effect is uncertain (antioxidants: RR 0.58, 95% CI 0.32 to 1.03; 1 trial, 18 participants; low-quality evidence. Medroxyprogesterone: RR 0.71, 95% CI 0.48 to 1.05; I² = 0%; 2 trials, 32 participants; low-quality evidence. Iron: RR 0.65, 95% CI 0.38 to 1.11; I² = 0%; 2 trials, 65 participants; low-quality evidence. R crenulata: RR 1.00, 95% CI 0.78 to 1.29; 1 trial, 125 participants; low-quality evidence). We found evidence of improvement of this risk with the administration of erythropoietin, but this information was extracted from a trial with issues related to risk of bias and imprecision (RR 0.41, 95% CI 0.20 to 0.84; 1 trial, 39 participants; very low-quality evidence). Regarding administration of ginkgo biloba, we did not perform a pooled estimation of RR for AMS due to considerable heterogeneity between the included studies (I² = 65%). RR estimates from the individual studies were conflicting (from 0.05 to 1.03; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 3. Other comparisonsWe found heterogeneous evidence regarding the risk of AMS when ginkgo biloba was compared with acetazolamide (I² = 63%). RR estimates from the individual studies were conflicting (estimations from 0.11 (95% CI 0.01 to 1.86) to 2.97 (95% CI 1.70 to 5.21); low-quality evidence). We found evidence of improvement when ginkgo biloba was administered along with acetazolamide, but this information was derived from a single trial with issues associated to risk of bias (compared to ginkgo biloba alone: RR 0.43, 95% CI 0.26 to 0.71; 1 trial, 311 participants; low-quality evidence). Administration of medroxyprogesterone plus acetazolamide did not improve the risk of AMS when compared to administration of medroxyprogesterone or acetazolamide alone (RR 1.33, 95% CI 0.50 to 3.55; 1 trial, 12 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.
AUTHORS' CONCLUSIONS
This Cochrane Review is the final in a series of three providing relevant information to clinicians, and other interested parties, on how to prevent high altitude illness. The assessment of non-pharmacological and miscellaneous interventions suggests that there is heterogeneous and even contradictory evidence related to the effectiveness of these prophylactic strategies. Safety of these interventions remains as an unclear issue due to lack of assessment. Overall, the evidence is limited due to its quality (low to very low), the relative paucity of that evidence and the number of studies pending classification for the three reviews belonging to this series (30 studies either awaiting classification or ongoing). Additional studies, especially those comparing with pharmacological alternatives (such as acetazolamide) are required, in order to establish or refute the strategies evaluated in this review.
Topics: Acetazolamide; Altitude Sickness; Brain Edema; Ginkgo biloba; Humans; Hypertension, Pulmonary; Medroxyprogesterone; Plant Extracts; Randomized Controlled Trials as Topic
PubMed: 31012483
DOI: 10.1002/14651858.CD013315 -
The European Journal of Contraception &... Apr 2019To evaluate the association between postpartum hormonal contraceptive use and postpartum depression.
PURPOSE
To evaluate the association between postpartum hormonal contraceptive use and postpartum depression.
MATERIALS AND METHODS
We searched the literature through March 2018 on the association between postpartum hormonal contraception use and incident postpartum depression. We used the United States Preventive Services Task Force framework to assess study quality.
RESULTS
Of 167 articles identified, four met inclusion criteria. Two studies found no differences in rates of postpartum depression between women using postpartum depot medroxyprogesterone and those not using hormonal contraception; however, a study of women receiving injectable norethisterone enanthate immediately postpartum found a 2-3-fold increased risk of depression at 6 weeks, though not at 3 months. One study compared combined hormonal contraception, progestin-only pills (POPs), etonogestrel implants and levonorgestrel intrauterine devices (LNG-IUDs) with no hormonal contraception, and found a 35-44% decreased risk of postpartum depression with POPs and LNG-IUDs, a small increased risk of postpartum antidepressant use among women using the etonogestrel implant and vaginal ring, and a decreased risk of antidepressant use with POPs.
CONCLUSIONS
Limited evidence found no consistent associations between hormonal contraceptive use and incidence of postpartum depression. Future research would be strengthened by using validated diagnostic measures, careful consideration of confounders, and ensuring adequate follow-up time.
Topics: Adult; Contraception; Contraception Behavior; Contraceptives, Oral, Hormonal; Depression, Postpartum; Female; Humans; Incidence; Postpartum Period; Pregnancy; Time Factors; Young Adult
PubMed: 30920314
DOI: 10.1080/13625187.2019.1569610 -
The Cochrane Database of Systematic... Dec 2018Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia....
BACKGROUND
Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia.
OBJECTIVES
To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
SEARCH METHODS
In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence.
MAIN RESULTS
We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia.Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13).Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported.
AUTHORS' CONCLUSIONS
We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
Topics: Administration, Oral; Endometrial Hyperplasia; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone; Randomized Controlled Trials as Topic
PubMed: 30521671
DOI: 10.1002/14651858.CD009458.pub3