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Frontiers in Psychiatry 2020The association between infertility treatments and mental disorders has been poorly addressed. This work aims to review current evidence on the psychopathological...
BACKGROUND
The association between infertility treatments and mental disorders has been poorly addressed. This work aims to review current evidence on the psychopathological effects of hormonal treatments used for infertility on women and the occurrence of newly diagnosed mood and psychotic disorders.
METHODS
A systematic review was performed by searching PubMed and clinicaltrials.gov databases from inception until September 2019. Clinical trials on hormone treatments for infertility in patients with mood or psychotic disorders, as well as those evaluating the onset of symptoms, were included. Selected studies were published in English, Spanish, and Dutch language peer-reviewed journals. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Observational studies and case reports were excluded. Effect sizes for changes in depressive symptoms were calculated with Hedges'g and Cohen's d confidence intervals. A meta-analysis was not performed due to the heterogeneity of hormonal compounds in protocols.
RESULTS
From 1,281 retrieved records, nine trials were included; all of them were conducted in non-clinical populations. Four trials compared Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists, showing a better mood profile for hormonal protocols including antagonists in one trial. Two trials compared protocols using GnRH agonists/antagonists versus natural cycle protocols (without gonadotropin stimulation), with a better mood profile (less depressive symptoms) in those protocols without gonadotropin stimulation. Other studies compared long and short protocols of GnRH agonists (no differences); two GnRH agonists, buserelin, and goserelin (no differences); and two patterns of clomiphene vs placebo administration (no differences). None of the selected studies investigated the risk of relapse in women with a previous diagnosis of depressive or psychotic disorders. When exploring pre-post changes in depressive symptoms, effect sizes suggested mild mood worsenings for most protocols (effect sizes ≤ -0.4), with the following pattern (worse to better): GnRH agonist > GnRH antagonist > no gonadotropin stimulation.
CONCLUSIONS
This is the first systematic review exploring the psychopathological effects of hormonal infertility treatments. Our study suggests that protocols without gonadotropin stimulation show a better mood profile when compared to those using GnRH antagonists or GnRH agonists. Future studies need to include patients with major mood and psychotic disorders.
PubMed: 32528332
DOI: 10.3389/fpsyt.2020.00479 -
The Cochrane Database of Systematic... Nov 2015Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during controlled ovarian hyperstimulation (COH) prior to planned oocyte retrieval, thus optimising the chances of live birth.
OBJECTIVES
To evaluate the effectiveness of the different GnRHa protocols as adjuncts to COH in women undergoing ART cycles.
SEARCH METHODS
We searched the following databases from inception to April 2015: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, CINAHL, PsycINFO, and registries of ongoing trials. Reference lists of relevant articles were also searched.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any two protocols of GnRHa used in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles in subfertile women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial eligibility and risk of bias, and extracted the data. The primary outcome measure was number of live births or ongoing pregnancies per woman/couple randomised. Secondary outcome measures were number of clinical pregnancies, number of oocytes retrieved, dose of gonadotrophins used, adverse effects (pregnancy losses, ovarian hyperstimulation, cycle cancellation, and premature luteinising hormone (LH) surges), and cost and acceptability of the regimens. We combined data to calculate odds ratios (OR) for dichotomous variables and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methods.
MAIN RESULTS
We included 37 RCTs (3872 women), one ongoing trial, and one trial awaiting classification. These trials made nine different comparisons between protocols. Twenty of the RCTs compared long protocols and short protocols. Only 19/37 RCTs reported live birth or ongoing pregnancy.There was no conclusive evidence of a difference between a long protocol and a short protocol in live birth and ongoing pregnancy rates (OR 1.30, 95% CI 0.94 to 1.81; 12 RCTs, n = 976 women, I² = 15%, low quality evidence). Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. There was evidence of an increase in clinical pregnancy rates (OR 1.50, 95% CI 1.18 to 1.92; 20 RCTs, n = 1643 women, I² = 27%, moderate quality evidence) associated with the use of a long protocol.There was no evidence of a difference between the groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort protocol (OR 1.78, 95% CI 0.72 to 4.36; one RCT, n = 150 women, low quality evidence), long luteal versus long follicular phase protocol (OR 1.89, 95% CI 0.87 to 4.10; one RCT, n = 223 women, low quality evidence), when GnRHa was stopped versus when it was continued (OR 0.75, 95% CI 0.42 to 1.33; three RCTs, n = 290 women, I² = 0%, low quality evidence), when the dose of GnRHa was reduced versus when the same dose was continued (OR 1.02, 95% CI 0.68 to 1.52; four RCTs, n = 407 women, I² = 0%, low quality evidence), when GnRHa was discontinued versus continued after human chorionic gonadotrophin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; one RCT, n = 181 women, low quality evidence), and when administration of GnRHa lasted for two versus three weeks before stimulation (OR 1.14, 95% CI 0.49 to 2.68; one RCT, n = 85 women, low quality evidence). Our primary outcomes were not reported for any other comparisons.Regarding adverse events, there were insufficient data to enable us to reach any conclusions except about the cycle cancellation rate. There was no conclusive evidence of a difference in cycle cancellation rate (OR 0.95, 95% CI 0.59 to 1.55; 11 RCTs, n = 1026 women, I² = 42%, low quality evidence) when a long protocol was compared with a short protocol. This suggests that in a population in which 9% of women would have their cycles cancelled using a short protocol, between 5.5% and 14% will have cancelled cycles when using a long protocol.The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years.
AUTHORS' CONCLUSIONS
When long GnRHa protocols and short GnRHa protocols were compared, we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates, but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects.
Topics: Buserelin; Clinical Protocols; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Live Birth; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Triptorelin Pamoate
PubMed: 26558801
DOI: 10.1002/14651858.CD006919.pub4 -
Evidence Report/technology Assessment... May 1999With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic... (Review)
Review
OBJECTIVES
With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis.
SEARCH STRATEGY
The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references.
SELECTION CRITERIA
We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included.
DATA COLLECTION AND ANALYSIS
The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine.
MAIN RESULTS
Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Cost-Benefit Analysis; Evidence-Based Medicine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 11098244
DOI: No ID Found -
Urologia Internationalis 2009The paper aims at evaluating the role of testosterone levels and their cut-off points in the treatment of prostate cancer with androgen deprivation therapy. (Review)
Review
INTRODUCTION
The paper aims at evaluating the role of testosterone levels and their cut-off points in the treatment of prostate cancer with androgen deprivation therapy.
MATERIALS AND METHODS
We performed a non-systematic review of the literature, searching Medline using the following key words: 'Prostatic neoplasms/therapy' [MeSH], 'Buserelin' [MeSH], 'Goserelin' [MeSH], 'Leuprolide' [MeSH], 'Triptorelin' [MeSH], 'prostate cancer*' [tiab], and 'testoster*' [tiab].
RESULTS
The most commonly used cut-off point of testosterone to define castration was 50 ng/dl. In this respect, GnRH agonists allowed castration in a very high percentage of patients (87.5-100%). Specifically, triptorelin was reported to yield castration level of testosterone in 98.8%, the classical formulation of leuprolide in 95-98.8% of the cases, and Eligard, a novel formulation of leuprolide, in 99-100%. With regard to the 20-ng/dl breakpoint, available data suggest that goserelin yields castration level of testosterone in 96%, the classical formulation of leuprolide in 87-92% of the patients, and the novel formulation in 88-97.5%.
CONCLUSIONS
The clinical significance of different levels of testosterone yielded during androgen deprivation therapy is still unknown. Considering the standard cut-off point of 50 ng/dl, GnRH agonists allowed castration in a very high percentage of patients.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers; Drug Monitoring; Gonadotropin-Releasing Hormone; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone; Treatment Outcome
PubMed: 19440008
DOI: 10.1159/000209352