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Archives of Gynecology and Obstetrics Apr 2024Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for... (Review)
Review
PURPOSE
Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer.
METHODS
Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review.
RESULTS
All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk.
CONCLUSION
There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
Topics: Female; Humans; Medroxyprogesterone Acetate; Delayed-Action Preparations; Breast Neoplasms; Contraceptive Agents, Female; Progestins
PubMed: 37966517
DOI: 10.1007/s00404-023-07265-5 -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
BMC Women's Health Oct 2021Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use.
METHODS
We searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes.
RESULTS
We identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10-1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider).
CONCLUSIONS
Self-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.
Topics: Community Health Workers; Contraceptive Agents, Female; Female; Humans; Injections; Medroxyprogesterone Acetate; Self Administration
PubMed: 34627229
DOI: 10.1186/s12905-021-01495-y -
Frontiers in Oncology 2022The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients...
BACKGROUND
The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.
STUDY DESIGN
Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".
RESULTS
A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.
CONCLUSIONS
Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.
PubMed: 36185260
DOI: 10.3389/fonc.2022.965029 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Male; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
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 -
Medicine Jun 2020Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed.
METHODS
This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018.
RESULTS
We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed.
CONCLUSION
This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.
Topics: Adenomyoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Conservative Treatment; Curettage; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Humans; Hysteroscopy; Medroxyprogesterone Acetate; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Pregnancy; Pregnancy Rate; Uterine Neoplasms
PubMed: 32590732
DOI: 10.1097/MD.0000000000020491 -
BioMed Research International 2023This systematic review was conducted to provide up-to-date evidence on the safety and effectiveness of task sharing in the delivery of modern contraceptives. . The... (Review)
Review
OBJECTIVE
This systematic review was conducted to provide up-to-date evidence on the safety and effectiveness of task sharing in the delivery of modern contraceptives. . The review followed the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. We searched Medline, Embase, Cochrane CENTRAL, and Google Scholar for peer-reviewed studies that reported on effectiveness and/or safety outcomes of task sharing of any modern contraceptive method. Only Cochrane Effective Practice of Organizations of Care (EPOC) study designs were eligible, and quality assessment of the evidence was performed using the Cochrane risk of bias (RoB) tools. Meta-analyses, where possible, were carried out using Stata, and certainty of the evidence for outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tool (GRADE).
RESULTS
Six studies met the inclusion criteria: five reported on self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) compared to administered by trained health providers; and one assessed tubal ligation performed by associate clinicians compared to advanced-level associate clinicians. Self-injection improved contraceptive continuation, with no increase in unintended pregnancy and no difference in side effects compared to provider administered. In tubal ligation, the rate of adverse events, time to complete procedure, and participant satisfaction were similar among associate clinicians and advanced clinicians.
CONCLUSION
The evidence suggests that self-injection of DMPA-SC and tubal ligation performed by associate clinicians are safe and effective. These findings should be complemented with the evidence on the feasibility and acceptability of task sharing of these methods. The review protocol was registered with PROSPERO CRD42021283336.
Topics: Pregnancy; Female; Humans; Family Planning Services; Contraception; Contraceptive Agents, Female; Subcutaneous Tissue; Research Design
PubMed: 36817856
DOI: 10.1155/2023/8735563 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
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