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International Journal of Molecular... Nov 2021The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and...
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.
The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients' serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.
Topics: Animals; B7-H1 Antigen; Cell Line, Tumor; Cytokines; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Killer Cells, Natural; Male; Mice; Programmed Cell Death 1 Receptor; Prostatic Neoplasms; T-Lymphocytes, Cytotoxic; Tumor Escape; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 34830209
DOI: 10.3390/ijms222212330 -
Frontiers in Pharmacology 2021Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and... (Review)
Review
Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown. To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites. The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence. Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26-1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29-1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization. Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.
PubMed: 34421586
DOI: 10.3389/fphar.2021.652979 -
The Cochrane Database of Systematic... Aug 2021Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is... (Review)
Review
BACKGROUND
Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is unclear how its effects compare to standard androgen suppression therapy.
OBJECTIVES
To assess the effects of degree compared with standard androgen suppression therapy for men with advanced hormone-sensitive prostate cancer.
SEARCH METHODS
We searched multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science, LILACS until September 2020), trial registries (until October 2020), and conference proceedings (until December 2020). We identified other potentially eligible trials by reference checking, citation searching, and contacting study authors.
SELECTION CRITERIA
We included randomized controlled trials comparing degarelix with standard androgen suppression therapy for men with advanced prostate cancer.
DATA COLLECTION AND ANALYSIS
Three review authors independently classified studies and abstracted data from the included studies. The primary outcomes were overall survival and serious adverse events. Secondary outcomes were quality of life, cancer-specific survival, clinical progression, other adverse events, and biochemical progression. We used a random-effects model for meta-analyses and assessed the certainty of evidence for the main outcomes according to GRADE.
MAIN RESULTS
We included 11 studies with a follow-up of between three and 14 months. We also identified five ongoing trials. Primary outcomes Data to evaluate overall survival were not available. Degarelix may result in little to no difference in serious adverse events compared to standard androgen suppression therapy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.62 to 1.05; low-certainty evidence; 2750 participants). Based on 114 serious adverse events in the standard androgen suppression group, this corresponds to 23 fewer serious adverse events per 1000 participants (43 fewer to 6 more). We downgraded the certainty of evidence for study limitations and imprecision. Secondary outcomes Degarelix likely results in little to no difference in quality of life assessed with a variety of validated questionnaires (standardized mean difference 0.06 higher, 95% CI 0.05 lower to 0.18 higher; moderate-certainty evidence; 2887 participants), with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Data to evaluate cancer-specific survival were not available. The effects of degarelix on cardiovascular events are very uncertain (RR 0.15, 95% CI 0.04 to 0.61; very low-certainty evidence; 80 participants). We downgraded the certainty of evidence for study limitations, imprecision, and indirectness as this trial was conducted in a unique group of high-risk participants with pre-existing cardiovascular morbidities. Degarelix likely results in an increase in injection site pain (RR 15.68, 95% CI 7.41 to 33.17; moderate-certainty evidence; 2670 participants). Based on 30 participants per 1000 with injection site pain with standard androgen suppression therapy, this corresponds to 440 more injection site pains per 1000 participants (192 more to 965 more). We downgraded the certainty of evidence for study limitations. We did not identify any relevant subgroup differences for different degarelix maintenance doses.
AUTHORS' CONCLUSIONS
We did not find trial evidence for overall survival or cancer-specific survival comparing degarelix to standard androgen suppression, but serious adverse events and quality of life may be similar between groups. The effects of degarelix on cardiovascular events are very uncertain as the only eligible study had limitations, was small with few events, and was conducted in a high-risk population. Degarelix likely results in an increase in injection site pain compared to standard androgen suppression therapy. Maximum follow-up of included studies was 14 months, which is short. There is a need for methodologically better designed and executed studies with long-term follow-up evaluating men with metastatic prostate cancer.
Topics: Disease Progression; Hormones; Humans; Male; Oligopeptides; Prostatic Neoplasms; Quality of Life
PubMed: 34350976
DOI: 10.1002/14651858.CD012548.pub2 -
Gynecological Endocrinology : the... Jul 2021The diagnostic accuracy of tests in identifying virilizing tumors in postmenopausal hyperandrogenism is limited. This systematic review compares the dexamethasone... (Comparative Study)
Comparative Study Meta-Analysis
Dexamethasone suppression test versus selective ovarian and adrenal vein catheterization in identifying virilizing tumors in postmenopausal hyperandrogenism - a systematic review and meta-analysis.
OBJECTIVE
The diagnostic accuracy of tests in identifying virilizing tumors in postmenopausal hyperandrogenism is limited. This systematic review compares the dexamethasone suppression test against selective ovarian and adrenal vein sampling of androgens in distinguishing neoplastic from non-neoplastic causes of postmenopausal hyperandrogenism.
METHODS
Diagnostic test accuracy studies on these index tests in postmenopausal women were selected based on pre-established criteria. The true positive, false positive, false negative, and true negative values were extracted and meta-analysis was conducted using the hierarchical summary receiver operator characteristics curve method.
RESULTS
The summary sensitivity of the dexamethasone suppression test is 100% (95% CI 0-100%) and that for selective venous sampling is 100% (95% CI 0-100%). The summary specificity of the dexamethasone suppression test is 89.2% (95% CI 85.3-92.2%) and that for selective venous sampling is 100% (95% CI 0.3-100%).
CONCLUSION
There is limited evidence for the use of dexamethasone suppression test or selective venous sampling in identifying virilizing tumors in postmenopausal hyperandrogenism.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Androgens; Catheterization, Peripheral; Dehydroepiandrosterone Sulfate; Dexamethasone; Diagnostic Techniques, Endocrine; Female; Glucocorticoids; Humans; Hyperandrogenism; Ovarian Neoplasms; Ovary; Postmenopause; Testosterone
PubMed: 33660585
DOI: 10.1080/09513590.2021.1897099 -
British Journal of Sports Medicine Aug 2021We systemically reviewed the literature to assess how long-term testosterone suppressing gender-affirming hormone therapy influenced lean body mass (LBM), muscular area,...
How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation.
OBJECTIVES
We systemically reviewed the literature to assess how long-term testosterone suppressing gender-affirming hormone therapy influenced lean body mass (LBM), muscular area, muscular strength and haemoglobin (Hgb)/haematocrit (HCT).
DESIGN
Systematic review.
DATA SOURCES
Four databases (BioMed Central, PubMed, Scopus and Web of Science) were searched in April 2020 for papers from 1999 to 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Eligible studies were those that measured at least one of the variables of interest, included transwomen and were written in English.
RESULTS
Twenty-four studies were identified and reviewed. Transwomen experienced significant decreases in all parameters measured, with different time courses noted. After 4 months of hormone therapy, transwomen have Hgb/HCT levels equivalent to those of cisgender women. After 12 months of hormone therapy, significant decreases in measures of strength, LBM and muscle area are observed. The effects of longer duration therapy (36 months) in eliciting further decrements in these measures are unclear due to paucity of data. Notwithstanding, values for strength, LBM and muscle area in transwomen remain above those of cisgender women, even after 36 months of hormone therapy.
CONCLUSION
In transwomen, hormone therapy rapidly reduces Hgb to levels seen in cisgender women. In contrast, hormone therapy decreases strength, LBM and muscle area, yet values remain above that observed in cisgender women, even after 36 months. These findings suggest that strength may be well preserved in transwomen during the first 3 years of hormone therapy.
Topics: Adipose Tissue; Androgen Antagonists; Athletic Performance; Body Composition; Cyproterone Acetate; Estradiol; Female; Hematocrit; Hemoglobin A; Humans; Male; Muscle Strength; Muscle, Skeletal; Sports; Testosterone; Time Factors; Transgender Persons; Transsexualism
PubMed: 33648944
DOI: 10.1136/bjsports-2020-103106 -
European Heart Journal. Cardiovascular... May 2022The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the...
AIMS
The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.
METHODS AND RESULTS
We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.
CONCLUSIONS
There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.
Topics: Androgen Antagonists; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostatic Neoplasms
PubMed: 33470403
DOI: 10.1093/ehjcvp/pvab005 -
The Cochrane Database of Systematic... Dec 2020The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.
PRIMARY OUTCOME MEASURES
live birth rate, incidence of ovarian hyperstimulation syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.
AUTHORS' CONCLUSIONS
This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33347618
DOI: 10.1002/14651858.CD006105.pub4 -
Maturitas Jan 2021Breast cancer survivors (BCS) usually receive treatments which lead to persistent oestrogen suppression, which may cause atrophic vaginitis in a large proportion of...
Breast cancer survivors (BCS) usually receive treatments which lead to persistent oestrogen suppression, which may cause atrophic vaginitis in a large proportion of these women. The most effective treatments for vulvovaginal atrophy (VVA) are based on local oestrogen therapy. However, these treatments are restricted in BCS due to the controversy over their use in women who had hormone-dependent tumours. Therefore, it is common to find untreated symptoms that affect sexual function and quality of life in BCS, thereby leading to the discontinuation of anti-oestrogenic treatments. This systematic review aims to discuss the current treatment options available for the genitourinary syndrome of menopause (GSM) in BCS. A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing treatment options for GSM or VVA in BCS up to April 2020. Studies evaluating treatments in different BCS cohorts were excluded. A total of 29 studies were finally included in the review. Non-hormonal treatments are the first-line treatment for VVA, but when these are not effective for symptom relief, other options can be considered, such as local oestrogen, erbium laser or CO2 laser and local androgens. The present data suggest that these therapies are effective for VVA in BCS; however, safety remains controversial and a major concern with all of these treatments.
Topics: Breast Neoplasms; Cancer Survivors; Female; Female Urogenital Diseases; Humans; Menopause; Observational Studies as Topic; Randomized Controlled Trials as Topic; Syndrome
PubMed: 33308636
DOI: 10.1016/j.maturitas.2020.08.010 -
European Urology Focus Sep 2021Bladder cancer demonstrates striking gender-based differences in incidence, with a role for androgens possibly implicated in the development and progression of the... (Review)
Review
CONTEXT
Bladder cancer demonstrates striking gender-based differences in incidence, with a role for androgens possibly implicated in the development and progression of the disease. Emerging preclinical and clinical evidence suggests that there may be a role for antiandrogen therapy in bladder cancer.
OBJECTIVE
This systematic review assessed the current clinical evidence evaluating androgen suppressive therapy (AST) for the treatment or prevention of bladder cancer.
EVIDENCE ACQUISITION
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, MEDLINE was searched for full-text articles detailing clinical outcomes or incidence of bladder cancer among patients who received AST, defined as gonadotropin-releasing hormone agonists or equivalent, androgen receptor antagonists, or 5-alpha reductase inhibitors.
EVIDENCE SYNTHESIS
A total of 12 studies were included. Five studies focused on prostate cancer patients, with one study in men with lower urinary tract symptoms. Among these studies, a lower incidence of bladder cancer was observed in five, with adjusted risk reduction estimates ranging from 7% to 47%. Six studies evaluating 11 820 bladder cancer patients investigated clinical outcomes among men who received a form of AST. Three out of four studies evaluating recurrence-free survival found a benefit for AST, with adjusted hazard ratios for recurrence of non-muscle-invasive cancer ranging from 0.29 to 0.53. Limitations included large variability in data sources and methodologies, as well as no data on tolerability.
CONCLUSIONS
Current evidence indicates that antiandrogen therapies exert a favorable influence on bladder tumors. Further prospective studies are needed to assess their therapeutic potential.
PATIENT SUMMARY
Androgen suppressive therapy is commonly prescribed for the treatment of prostate-related problems. Prior research indicates that there may be a role for these treatments in patients with bladder cancer. In this review, we evaluate the current evidence that strongly suggests that these agents may be effective against bladder cancer.
Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Androgens; Carcinoma in Situ; Humans; Male; Prostatic Neoplasms; Urinary Bladder Neoplasms
PubMed: 33132108
DOI: 10.1016/j.euf.2020.10.002 -
Human Reproduction Update Jan 2021Although surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical therapy in preventing recurrence of endometriosis following surgery.
OBJECTIVE AND RATIONALE
We performed a review of prospective observational studies and randomised controlled trials (RCTs) to evaluate the risk of endometriosis recurrence in patients undergoing post-operative hormonal suppression, compared to placebo/expectant management.
SEARCH METHODS
The following databases were searched from inception to March 2020 for RCTs and prospective observational cohort studies: MEDLINE, Embase, Cochrane CENTRAL and Web of Science. We included English language full-text articles of pre-menopausal women undergoing conservative surgery (conserving at least one ovary) and initiating hormonal suppression within 6 weeks post-operatively with either combined hormonal contraceptives (CHC), progestins, androgens, levonorgesterel-releasing intra-uterine system (LNG-IUS) or GnRH agonist or antagonist. We excluded from the final analysis studies with <12 months of follow-up, interventions of diagnostic laparoscopy, experimental/non-hormonal treatments or combined hormonal therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies.
OUTCOMES
We included 17 studies (13 RCTs and 4 cohort studies), with 2137 patients (1189 receiving post-operative suppression and 948 controls), which evaluated various agents: CHC (6 studies, n = 869), progestin (3 studies, n = 183), LNG-IUS (2 studies, n = 94) and GnRH agonist (9 studies, n = 1237). The primary outcome was post-operative endometriosis recurrence, determined by imaging or recurrence of symptoms, at least 12 months post-operatively. The secondary outcome was change in endometriosis-related pain. Mean follow up of included studies ranged from 12 to 36 months, and outcomes were assessed at a median of 18 months. There was a significantly decreased risk of endometriosis recurrence in patients receiving post-operative hormonal suppression compared to expectant management/placebo (relative risk (RR) 0.41, 95% CI: 0.26 to 0.65), 14 studies, 1766 patients, I2 = 68%, random effects model). Subgroup analysis on patients treated with CHC and LNG-IUS as well as sensitivity analyses limited to RCTs and high-quality studies showed a consistent decreased risk of endometriosis recurrence. Additionally, the patients receiving post-operative hormonal suppression had significantly lower pain scores compared to controls (SMD -0.49, 95% CI: -0.91 to -0.07, 7 studies, 652 patients, I2 = 68%).
WIDER IMPLICATIONS
Hormonal suppression should be considered for patients not seeking pregnancy immediately after endometriosis surgery in order to reduce disease recurrence and pain. Various hormonal agents have been shown to be effective, and the exact treatment choice should be individualised according to each woman's needs.
Topics: Endometriosis; Female; Humans; Observational Studies as Topic; Pregnancy; Progestins; Recurrence
PubMed: 33020832
DOI: 10.1093/humupd/dmaa033