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Fertility and Sterility Apr 2017To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI).
DESIGN
An updated systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Patients undergoing OI-IUI for infertility.
INTERVENTION(S)
Exogenous P luteal support after OI-IUI.
MAIN OUTCOME MEASURE(S)
Live birth.
RESULT(S)
Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76).
CONCLUSION(S)
Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins.
Topics: Female; Fertility; Fertility Agents; Gonadotropins; Humans; Infertility; Insemination, Artificial; Live Birth; Luteal Phase; Odds Ratio; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Risk Factors; Treatment Outcome
PubMed: 28238492
DOI: 10.1016/j.fertnstert.2017.01.011 -
Sleep Medicine Reviews Dec 2022Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly... (Review)
Review
Sleep disturbance is a common clinical concern throughout the menopausal transition. However, the pathophysiology and causes of these sleep disturbances remain poorly understood, making it challenging to provide appropriate therapy. Our goal was to i) review the literature about the influence of ovarian hormones on sleep in perimenopausal women, ii) summarize the potential underlying pathophysiology of menopausal sleep disturbances and iii) evaluate the implications of these findings for the therapeutic approach to sleep disturbances in the context of menopause. A systematic literature search using the databases Embase, MEDLINE and Cochrane Library was conducted. Keywords relating to ovarian hormones, sleep disturbances and menopause were used. Ultimately, 86 studies were included. Study Quality Assessment Tools of the National Institutes of Health were used for quality assessment. Results from good-quality studies demonstrated that the postmenopausal decline in estrogen and progesterone contributes to sleep disturbances in women and that timely treatment with estrogen and/or progesterone therapy improved overall sleep quality. Direct and indirect effects of both hormones acting in the central nervous system and periphery, as well as via secondary effects (e.g. reduction in vasomotor symptoms), can contribute to improvements in sleep. To strengthen external validity, studies examining neurobiological pathways are needed.
Topics: United States; Female; Humans; Progesterone; Sleep; Estrogens
PubMed: 36356400
DOI: 10.1016/j.smrv.2022.101710 -
The Cochrane Database of Systematic... Mar 2012About 5% of women experience severe symptoms called premenstrual syndrome (PMS), only in the two weeks before their menstrual periods. Treatment with progesterone may... (Review)
Review
BACKGROUND
About 5% of women experience severe symptoms called premenstrual syndrome (PMS), only in the two weeks before their menstrual periods. Treatment with progesterone may restore a deficiency, balance menstrual hormone levels or reduce effects of falling progesterone levels on the brain or on electrolytes in the blood.
OBJECTIVES
The objectives were to determine if progesterone has been found to be an effective treatment for all or some premenstrual symptoms and if adverse events associated with this treatment have been reported.
SEARCH METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to February 2011. We contacted pharmaceutical companies for information about unpublished trials, for the first version of this review.The search strings are in Appendix 2.
SELECTION CRITERIA
We included randomised double-blind, placebo-controlled trials of progesterone on women with PMS diagnosed by at least two prospective cycles, without current psychiatric disorder.
DATA COLLECTION AND ANALYSIS
Two reviewers (BM and OF) extracted data independently and decided which trials to include. OF wrote to trial investigators for missing data.
MAIN RESULTS
From 17 studies, only two met our inclusion criteria. Together they had 280 participants aged between 18 and 45 years. One hundred and fifteen yielded analysable results. Both studies measured symptom severity using subjective scales. Differing in design, participants, dose of progesterone and how delivered, the studies could not be combined in meta-analysis.Adverse events which may or may not have been side effects of the treatment were described as mild.Both trials had defects. They intended to exclude women whose symptoms continued after their periods. When data from ineligible women were excluded from analysis in one trial, the other women were found to have benefited more from progesterone than placebo. The smaller study found no statistically significant difference between oral progesterone, vaginally absorbed progesterone and placebo, but reported outcomes incompletely.
AUTHORS' CONCLUSIONS
The trials did not show that progesterone is an effective treatment for PMS nor that it is not. Neither trial distinguished a subgroup of women who benefited, nor examined claimed success with high doses.
Topics: Female; Humans; Premenstrual Syndrome; Progesterone; Progestins; Randomized Controlled Trials as Topic
PubMed: 22419287
DOI: 10.1002/14651858.CD003415.pub4 -
European Review For Medical and... Jan 2017Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general... (Review)
Review
OBJECTIVE
Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population - approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.
MATERIALS AND METHODS
A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.
RESULTS
The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.
CONCLUSIONS
The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.
Topics: Cytochrome P-450 CYP1B1; Female; Fibrillins; Hashimoto Disease; Humans; Polycystic Ovary Syndrome; Receptors, LHRH; Transforming Growth Factor beta
PubMed: 28165551
DOI: No ID Found -
Neuro-oncology Advances 2021Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of... (Review)
Review
BACKGROUND
Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients.
METHODS
Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates.
RESULTS
15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%).
CONCLUSIONS
BCBM exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.
PubMed: 33898990
DOI: 10.1093/noajnl/vdab010 -
Oral progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis.American Journal of Obstetrics &... Mar 2019The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other... (Meta-Analysis)
Meta-Analysis
OBJECTIVE DATA
The purpose of this study was to perform a systematic review and metaanalysis of randomized controlled trials on oral progesterone compared with placebo or other interventions for preterm birth prevention in singleton pregnancies with previous spontaneous preterm birth. The primary outcome was preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth rate at <34 weeks gestation, neonatal morbidity/death, and maternal side-effects.
STUDY
Searches were performed in PubMed, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Register with the use of a combination of words related to "preterm birth," "preterm delivery," "progesterone," "progestogens," and "oral" from inception of each database to April 2018. Additionally, systematic reviews on progesterone for preterm birth prevention that were identified in our search were also reviewed for additional studies. We included all randomized trials of asymptomatic singleton gestations with previous spontaneous singleton preterm birth that had been randomized to prophylactic treatment with oral progesterone vs placebo, no treatment, or other preterm birth intervention. Exclusion criteria included quasirandomized trials, trials that involved women with preterm labor/membrane rupture at the time of randomization or multiple gestations.
STUDY APPRAISAL AND SYNTHESIS METHODS
The risk of bias and quality of evidence were assessed for each study. All analyses were done with an intention-to-treat approach. The primary outcome was incidence of preterm birth at <37 weeks gestation; the secondary outcomes included preterm birth at <34 and <28 weeks gestation, maternal adverse events, maternal serum progesterone level, and neonatal morbidity and death. Summary measures were reported as relative risk or mean difference. I >30% was used to identify heterogeneity.
RESULTS
The search strategy identified 79 distinct studies. Three trials on oral progesterone vs placebo (involved 386 patients: 196 in oral progesterone and 190 in placebo) met the inclusion criteria; there were no studies on oral progesterone vs other intervention that met inclusion criteria. Metaanalysis demonstrated a significantly decreased risk of preterm birth at <37 weeks gestation (42% vs 63%; =.0005; relative risk, 0.68; 95% confidence interval, 0.55-0.84), preterm birth at <34 weeks gestation (29% vs 53%; <.00001; relative risk, 0.55; 95% confidence interval, 0.43-0.71), and increased gestational age of delivery (mean difference, 1.71 weeks; 95% confidence interval, 1.11-2.30) with oral progesterone compared with placebo. There was a significantly lower rate of perinatal death (5% vs 17%; =.001; relative risk 0.32; 95% confidence interval, 0.16-0.63), neonatal intensive care admission (relative risk, 0.39; 95% confidence interval, 0.25-0.61), respiratory distress syndrome (relative risk, 0.21; 95% confidence interval, 0.05-0.93), and higher birthweight (mean difference, 435.06 g; 95% confidence interval, 324.59-545.52) with oral progesterone. There was a higher rate of maternal adverse effects with oral progesterone that included dizziness (relative risk, 2.95; 95% confidence interval, 1.47-5.90), somnolence (relative risk, 2.06; 95% confidence interval, 1.29-3.30), and vaginal dryness (relative risk, 2.37; 95% confidence interval, 1.10-5.11); no serious adverse effects were noted.
CONCLUSION
Oral progesterone appears to be effective for the prevention of recurrent preterm birth and a reduction in perinatal morbidity and mortality rates in asymptomatic singleton gestations with a history of previous spontaneous preterm birth compared with placebo. There were also increased adverse effects with oral progesterone therapy compared with placebo, although none were serious. Further randomized study on oral progesterone compared with other established therapies for the prevention of recurrent preterm birth are warranted.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pregnancy, Multiple; Premature Birth; Progesterone; Progestins
PubMed: 31172132
DOI: 10.1016/j.ajogmf.2019.03.001 -
Reviews in Endocrine & Metabolic... Apr 2023Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity... (Review)
Review
Periconceptional maternal obesity is linked to adverse maternal and neonatal outcomes. Identifying periconceptional biomarkers of pathways affected by maternal obesity can unravel pathophysiologic mechanisms and identify individuals at risk of adverse clinical outcomes. The literature was systematically reviewed to identify periconceptional biomarkers of the endocrine, inflammatory and one-carbon metabolic pathways influenced by maternal obesity. A search was conducted in Embase, Ovid Medline All, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases, complemented by manual search in PubMed until December 31, 2020. Eligible studies were those that measured biomarker(s) in relation to maternal obesity, overweight/obesity or body mass index (BMI) during the periconceptional period (14 weeks preconception until 14 weeks post conception). The ErasmusAGE score was used to assess the quality of included studies. Fifty-one articles were included that evaluated over 40 biomarkers. Endocrine biomarkers associated with maternal obesity included leptin, insulin, thyroid stimulating hormone, adiponectin, progesterone, free T4 and human chorionic gonadotropin. C-reactive protein was associated with obesity as part of the inflammatory pathway, while the associated one-carbon metabolism biomarkers were folate and vitamin B12. BMI was positively associated with leptin, C-reactive protein and insulin resistance, and negatively associated with Free T4, progesterone and human chorionic gonadotropin. Concerning the remaining studied biomarkers, strong conclusions could not be established due to limited or contradictory data. Future research should focus on determining the predictive value of the optimal set of biomarkers for their use in clinical settings. The most promising biomarkers include leptin, adiponectin, human chorionic gonadotropin, insulin, progesterone and CRP.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Leptin; C-Reactive Protein; Obesity, Maternal; Adiponectin; Progesterone; Obesity; Biomarkers; Insulin; Chorionic Gonadotropin; Carbon
PubMed: 36520252
DOI: 10.1007/s11154-022-09762-5 -
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 -
Frontiers in Neuroendocrinology Jan 2021Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior... (Review)
Review
Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior and mental health. Throughout the reproductive years, estrogens and progesterone levels fluctuate across the menstrual cycle and can modulate neural circuits involved in affective and cognitive processes. Here, we review seventy-seven neuroimaging studies and provide a comprehensive and data-driven evaluation of the accumulating evidence on brain plasticity associated with endogenous ovarian hormone fluctuations in naturally cycling women (n = 1304). The results particularly suggest modulatory effects of ovarian hormones fluctuations on the reactivity and structure of cortico-limbic brain regions. These findings highlight the importance of performing multimodal neuroimaging studies on neural correlates of systematic ovarian hormone fluctuations in naturally cycling women based on careful menstrual cycle staging.
Topics: Brain; Estrogens; Female; Humans; Menstrual Cycle; Neuroimaging; Progesterone
PubMed: 33098847
DOI: 10.1016/j.yfrne.2020.100878 -
Reproductive Sciences (Thousand Oaks,... Jan 2023This study was to assess the effectiveness of cervical pessary combined with vaginal progesterone for the prevention of preterm birth (PTB). Ten studies about singleton... (Meta-Analysis)
Meta-Analysis Review
This study was to assess the effectiveness of cervical pessary combined with vaginal progesterone for the prevention of preterm birth (PTB). Ten studies about singleton [five randomized controlled trials (RCTs), vs vaginal progesterone; four cohorts, vs vaginal progesterone; two cohorts, vs cervical cerclage + vaginal progesterone] and two cohort studies about multiple pregnancies (vs vaginal progesterone) were included after searching electronic databases. For singleton pregnancies, the meta-analysis of three non-RCTs [relative risk (RR) = 0.41, p = 0.001] or total trials in non-Asian country (RR = 0.56, p = 0.03) revealed that compared with vaginal progesterone alone, cervical pessary + vaginal progesterone treatment had significant effectiveness on preventing PTB < 34 weeks, but not for five RCTs; meta-analysis of two trials showed that cervical pessary + vaginal progesterone had no significant prevention effects of PTB compared with cervical cerclage + vaginal progesterone. For multiple pregnancies, meta-analysis of two trials showed that compared with vaginal progesterone, cervical pessary + vaginal progesterone treatment increased neonatal birth weight (standardized mean difference = 0.50, p = 0.01). Trial sequential analysis implied additional studies were required. Four studies vs other controls (pessary, three-combined, tocolysis, conservative or no treatment; one study, each) were selected for systematic review. In conclusion, cervical pessary combined with vaginal progesterone may be safe and effective to prevent PTB in singleton pregnancies and increase neonatal birth weight in the multiple pregnancies compared with vaginal progesterone alone.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Progesterone; Premature Birth; Pessaries; Birth Weight; Cervix Uteri; Administration, Intravaginal
PubMed: 35352330
DOI: 10.1007/s43032-022-00926-x