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Sexually Transmitted Diseases May 2019Evidence suggests that some forms of hormonal contraception (HC) increase women's risk of non-human immunodeficiency virus sexually transmitted infections (STIs), yet... (Comparative Study)
Comparative Study
BACKGROUND
Evidence suggests that some forms of hormonal contraception (HC) increase women's risk of non-human immunodeficiency virus sexually transmitted infections (STIs), yet evidence has not been reviewed since 2008. We conducted an updated systematic review to incorporate studies published between January 2009 and June 2017 to examine the relationship between HCs and incident or recurrent STIs.
METHODS
We searched PubMed and EMBASE to identify prospective studies comparing risk of Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Trichomonas vaginalis, between women using HC versus nonhormonal methods or no methods. We summarize results by type of STI and HC and study quality using an adapted Newcastle-Ottawa Quality Assessment Scale.
RESULTS
Thirty articles met the inclusion criteria. Depo-medroxyprogesterone acetate (DMPA) reduces the risk of trichomoniasis (consistent evidence) and may increase the risk of HSV-2 (strong effect, few studies); inconclusive evidence exists for HPV, chlamydia, gonorrhea, and syphilis. Data on oral contraceptive pills (OCPs; generally not differentiated whether combined or progestin-only pills) suggest that use is associated with a reduced risk of trichomoniasis with inconclusive findings for HSV-2, HPV, chlamydia, gonorrhea, and syphilis. Very few studies included norethisterone enanthate (Net-En) injectable, implants or the levonorgestrel intrauterine device.
CONCLUSIONS
Depo-medroxyprogesterone acetate and OCPs reduce the risk of trichomoniasis and DMPA may increase the risk of HSV-2. However, the potential for confounding cannot be ruled out. Future studies should specify the type of injectable or OCP used to increase understanding of biological pathways; more research is needed on implants and hormonal intrauterine devices.
Topics: Contraceptives, Oral, Hormonal; Female; Herpes Genitalis; Humans; Medroxyprogesterone Acetate; Prospective Studies; Risk; Risk Assessment; Sexually Transmitted Diseases; Trichomonas Infections
PubMed: 30628946
DOI: 10.1097/OLQ.0000000000000975 -
Current Medical Research and Opinion Mar 2022The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms...
OBJECTIVE
The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms and quality of life.
METHODS
A literature search of PubMed, Ovid (MEDLINE and EMBASE), and Web of Science was performed from inception to December 2020. In addition, a targeted search of cited references was also performed. Our search identified 330 articles of which 17 were deemed eligible for full-text review. Eligible studies included randomized control trials, observational studies, and case series with at least 5 cases, investigating the effect of progestin subdermal implants on endometriosis-related pain scores in women of reproductive age with a clinical, radiologic, or surgical diagnosis of endometriosis. Six articles were excluded after the full-text screen.
RESULTS
Eleven articles describing a total of 335 patients were eligible for inclusion. Across all studies, etonogestrel- and segesterone-releasing progestin subdermal implants improved VAS pain scores for cyclic pelvic pain/dysmenorrhea (VAS at baseline ranged from 6.1 to 7.5 cm and after treatment from 1.7 to 4.9 cm, = 121), non-cyclic pelvic pain (baseline VAS 7.2-7.6 cm and after treatment 2.0-3.7 cm, = 96) and dyspareunia (baseline VAS 1.61-8.3 cm and after treatment 1.0-7.1 cm, = 87). Symptom improvement with the progestin subdermal implant was equivalent to treatment with depot medroxyprogesterone acetate (DMPA; average baseline VAS 6.5 and after DMPA treatment 3.0, compared to 2.0 after treatment with the implant) or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS; baseline cyclic and non-cyclic pain scores 7.3 and 7.4 respectively decreased to 1.9 and 1.9 after LNG-IUS treatment). Improvements were also demonstrated in quality-of-life scores (average improvement of 36% in all domains of the Endometriosis Health Profile-30 and significant improvements in social functioning, general health, bodily pain, vitality and mental health domains on the Short Form-36 questionnaire) and sexual function (total sexual function score improved from 24 to 25.35 and 26.25 at 6 and 12 months).
CONCLUSION
Etonogestrel- and segesterone-releasing progestin subdermal implants appear to improve endometriosis-related pain symptoms and quality of life and may provide an additional component in the management of endometriosis. However, this systematic review is limited by the small sample size and heterogeneity in the data. As such, larger prospective randomized trials are needed to guide further management.
PROSPERO REGISTRATION
CRD42021225665.
Topics: Endometriosis; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pelvic Pain; Progestins; Prospective Studies; Quality of Life
PubMed: 35048754
DOI: 10.1080/03007995.2022.2031144 -
The Cochrane Database of Systematic... Jun 2020Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other factors, the severity of the symptoms, a woman's age, her wish to get pregnant, and the presence of other pathologies. Heavy menstrual bleeding was classically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. Currently the definition is based on the woman's perception of excessive bleeding which is affecting her quality of life. The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss: users of the levonorgestrel-releasing intrauterine system (LNG-IUS) reported reductions of up to 90%. Insertion may, however, be regarded as invasive by some women, which affects its acceptability.
OBJECTIVES
To determine the effectiveness, acceptability and safety of progestogen-releasing intrauterine devices in reducing heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in women of reproductive age treated with LNG-IUS devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the certainty of evidence.
MAIN RESULTS
We included 25 RCTs (2511 women). Limitations in the evidence included risk of attrition bias and low numbers of participants. The studies compared the following interventions. LNG-IUS versus other medical therapy The other medical therapies were norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pill, mefenamic acid, tranexamic acid or usual medical treatment (where participants could choose the oral treatment that was most suitable). The LNG-IUS may improve HMB, lowering menstrual blood loss according to the alkaline haematin method (mean difference (MD) 66.91 mL, 95% confidence interval (CI) 42.61 to 91.20; 2 studies, 170 women; low-certainty evidence); and the Pictorial Bleeding Assessment Chart (MD 55.05, 95% CI 27.83 to 82.28; 3 studies, 335 women; low-certainty evidence). We are uncertain whether the LNG-IUS may have any effect on women's satisfaction up to one year (RR 1.28, 95% CI 1.01 to 1.63; 3 studies, 141 women; I² = 0%, very low-certainty evidence). The LNG-IUS probably leads to slightly higher quality of life measured with the SF-36 compared with other medical therapy if (MD 2.90, 95% CI 0.06 to 5.74; 1 study: 571 women; moderate-certainty evidence) or with the Menorrhagia Multi-Attribute Scale (MD 13.40, 95% CI 9.89 to 16.91; 1 trial, 571 women; moderate-certainty evidence). The LNG-IUS and other medical therapies probably give rise to similar numbers of women with serious adverse events (RR 0.91, 95% CI 0.63 to 1.30; 1 study, 571 women; moderate-certainty evidence). Women using other medical therapy are probably more likely to withdraw from treatment for any reason (RR 0.49, 95% CI 0.39 to 0.60; 1 study, 571 women, moderate-certainty evidence) and to experience treatment failure than women with LNG-IUS (RR 0.34, 95% CI 0.26 to 0.44; 6 studies, 535 women; moderate-certainty evidence). LNG-IUS versus endometrial resection or ablation (EA) Bleeding outcome results are inconsistent. We are uncertain of the effect of the LNG-IUS compared to EA on rates of amenorrhoea (RR 1.21, 95% CI 0.85 to 1.72; 8 studies, 431 women; I² = 21%; low-certainty evidence) and hypomenorrhoea (RR 0.98, 95% CI 0.73 to 1.33; 4 studies, 200 women; low-certainty evidence) and eumenorrhoea (RR 0.55, 95% CI 0.30 to 1.00; 3 studies, 160 women; very low-certainty evidence). We are uncertain whether both treatments may have similar rates of satisfaction with treatment at 12 months (RR 0.95, 95% CI 0.85 to 1.07; 5 studies, 317 women; low-certainty evidence). We are uncertain if the LNG-IUS compared to EA has any effect on quality of life, measured with SF-36 (MD -14.40, 95% CI -22.63 to -6.17; 1 study, 33 women; very low-certainty evidence). Women with the LNG-IUS compared with EA are probably more likely to have any adverse event (RR 2.06, 95% CI 1.44 to 2.94; 3 studies, 201 women; moderate-certainty evidence). Women with the LNG-IUS may experience more treatment failure compared to EA at one year follow up (persistent HMB or requirement of additional treatment) (RR 1.78, 95% CI 1.09 to 2.90; 5 studies, 320 women; low-certainty evidence); or requirement of hysterectomy may be higher at one year follow up (RR 2.56, 95% CI 1.48 to 4.42; 3 studies, 400 women; low-certainty evidence). LNG-IUS versus hysterectomy We are uncertain whether the LNG-IUS has any effect on HMB compared with hysterectomy (RR for amenorrhoea 0.52, 95% CI 0.39 to 0.70; 1 study, 75 women; very low-certainty evidence). We are uncertain whether there is difference between LNG-IUS and hysterectomy in satisfaction at five years (RR 1.01, 95% CI 0.94 to 1.08; 1 study, 232 women; low-certainty evidence) and quality of life (SF-36 MD 2.20, 95% CI -2.93 to 7.33; 1 study, 221 women; low-certainty evidence). Women in the LNG-IUS group may be more likely to have treatment failure requiring hysterectomy for HMB at 1-year follow-up compared to the hysterectomy group (RR 48.18, 95% CI 2.96 to 783.22; 1 study, 236 women; low-certainty evidence). None of the studies reported cost data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The LNG-IUS may improve HMB and quality of life compared to other medical therapy; the LNG-IUS is probably similar for HMB compared to endometrial destruction techniques; and we are uncertain if it is better or worse than hysterectomy. The LNG-IUS probably has similar serious adverse events to other medical therapy and it is more likely to have any adverse events than EA.
Topics: Antifibrinolytic Agents; Contraceptives, Oral; Endometrium; Female; Humans; Hysterectomy; Intrauterine Devices, Medicated; Levonorgestrel; Mefenamic Acid; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome
PubMed: 32529637
DOI: 10.1002/14651858.CD002126.pub4 -
Contraception Jun 2018We performed a systematic review to look for an association between progestin-only contraception and depression.
OBJECTIVE
We performed a systematic review to look for an association between progestin-only contraception and depression.
METHODS
We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders.
RESULTS
We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression.
CONCLUSION
Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).
Topics: Contraception; Depression; Drug Implants; Female; Humans; Injections, Intramuscular; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone Acetate; Progestins
PubMed: 29496297
DOI: 10.1016/j.contraception.2018.01.010 -
Human Reproduction Update Feb 2020Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the effectiveness of abortifacient drugs or result in other adverse outcomes.
OBJECTIVE AND RATIONALE
We undertook two systematic reviews to examine the early administration of LARCs in women undergoing medical abortion with mifepristone and misoprostol. (i) For women who are having a medical abortion and who plan to use a progestogen-only contraceptive implant or injectable, does administration of the contraception at the same time as mifepristone influence the efficacy of the abortion? (Implant/injectable review). (ii) For women who have had a medical abortion, how soon after expulsion of the products of conception is it safe to insert an intrauterine contraceptive device/system? (LNG-IUS/Cu-IUD review).
SEARCH METHODS
On 19 November 2018, we searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily and Epub Ahead-of-Print, In-Process and Other Non-Indexed Citations; the Cochrane Library; Cinahl Plus; and Web of Science Core Collection. Eligible studies were randomised controlled trials (RCTs), in English from 1985 (Implant/injectable review) or 2007 (LNG-IUS/Cu-IUD review) onwards, conducted in women undergoing medical abortion with mifepristone and misoprostol and studying either (i) simultaneous administration of mifepristone and a progestogen-only contraceptive implant or injectable compared to administration >24 h after mifepristone, or (ii) immediate insertion of intrauterine contraception after expulsion of the products of conception compared to early insertion (≤7 days) or to delayed insertion (>7 days) or early compared to delayed insertion. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for RCTs. All the outcomes were analysed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed-effect model. The overall quality of the evidence was assessed using GRADE.
OUTCOMES
Two RCTs (n = 1027) showed lower 'subsequent unintended pregnancy' rates and higher 'patient satisfaction' rates, and no other differences, after simultaneous administration of mifepristone and the implant compared to delayed administration. One RCT (n = 461) showed higher 'patient satisfaction' rates after simultaneous administration than after delayed administration of mifepristone and the injectable, but no other differences between these interventions. Three RCTs (n = 536) found no differences other than higher copper IUC uptake after early compared to delayed insertion at ≤9 weeks of gestation and higher rates of IUC expulsion, continuation and uptake after immediate compared to delayed insertion at 9+1-12+0 weeks of gestation and higher IUC continuation rates after immediate compared to delayed insertion at 12+1-20+0 weeks of gestation. The quality of this evidence ranged from very low to high and was mainly compromised by low event rates, high attrition and no blinding.
WIDER IMPLICATIONS
The contraceptive implant or injectable should be offered on the day of taking mifepristone. Intrauterine methods of contraception should be offered as soon as possible after expulsion of the pregnancy.
Topics: Abortion, Induced; Female; Humans; Intrauterine Devices; Long-Acting Reversible Contraception; Mifepristone; Postoperative Care; Pregnancy; Pregnancy, Unplanned; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 32096862
DOI: 10.1093/humupd/dmz040 -
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 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... Nov 2019Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen.
OBJECTIVES
To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight.
SEARCH METHODS
In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE.
SELECTION CRITERIA
All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures.
DATA COLLECTION AND ANALYSIS
We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated.
MAIN RESULTS
We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome. Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36). Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38). Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73). Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly.
AUTHORS' CONCLUSIONS
Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods. We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).
Topics: Blood Glucose; Carbohydrate Metabolism; Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Dietary Carbohydrates; Fasting; Female; Humans; Insulin; Overweight; Randomized Controlled Trials as Topic
PubMed: 31711271
DOI: 10.1002/14651858.CD006133.pub5 -
Journal of Musculoskeletal & Neuronal... Sep 2017To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD)... (Meta-Analysis)
Meta-Analysis Review
Estrogen-progestin therapy causes a greater increase in spinal bone mineral density than estrogen therapy - a systematic review and meta-analysis of controlled trials with direct randomization.
OBJECTIVE
To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD) in randomized controlled trials (RCT) with direct randomization to estrogen (ET) or estrogen-progestin (EPT) therapy.
METHODS
Systematic literature searches in biomedical databases identified RCT with direct randomization and parallel estrogen doses that measured spinal BMD change/year. Cyclic P4/P was included in this random effects meta-analysis only if for ≥ half the number of E-days.
RESULTS
Searches yielded 155 publications; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women. Women averaged mid-50 years, ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate (MPA). The weighted mean EPT minus ET percentage difference in spinal BMD change was +0.68%/year (95% CI 0.38, 0.97%) (P=0.00001). This result was highly heterogeneous (I²=81%) but this may reflect the small number of studies.
CONCLUSION
Estrogen with an osteoblast P4R-acting progestin (EPT) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET. These data have implications for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women.
Topics: Bone Density; Estrogens; Female; Humans; Osteoporosis, Postmenopausal; Progestins; Randomized Controlled Trials as Topic
PubMed: 28860416
DOI: No ID Found -
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