-
Frontiers in Endocrinology 2022Although using letrozole (LE) during fertilisation and intracytoplasmic sperm injection (IVF/ICSI) has many advantages, it remains unclear whether LE induces an...
Although using letrozole (LE) during fertilisation and intracytoplasmic sperm injection (IVF/ICSI) has many advantages, it remains unclear whether LE induces an increase in progestogen during the late follicular phase. The objective of this study was to investigate whether progesterone levels increased under antagonist protocols supplemented with LE on the trigger day using a retrospective cohort study. The study included 1,133 women who underwent IVF/ICSI cycles from January 2018 to June 2020. After propensity score matching (PSM) for baseline characteristics, 266 patients with gonadotropin-releasing hormone-antagonist (GnRH-ant) were matched to 266 patients with letrozole + GnRH-ant (LE GnRH-ant) (PSM 1 cohort), and 283 patients with gonadotropin-releasing hormone-agonist (GnRH-a) were matched to 283 patients with LE GnRH-ant (PSM 2 cohort). In the PSM 1 cohort, patients in the LE GnRH-a group presented higher progesterone levels (1.22 ± 0.95 ng/mL vs 0.86 ± 0.60 ng/mL, < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (24.81% vs 7.52%, < 0.001). In PSM 2 cohort, patients in the LE GnRH-a group presented higher progesterone levels on trigger day (1.23 ± 0.91 ng/mL vs 0.98 ± 0.61 ng/mL, < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (25.45% vs 12.70%, < 0.001). In the PSM 1 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL, with an increase in every retrieved oocyte in the LE GnRH-ant group (β 0.05 ng/mL [95% CI 0.04, 0.06], < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-ant group (β 0.02 ng/mL [95% CI 0.01, 0.03], < 0.001), with for interaction being 0.0018. In the PSM 2 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL with an increase in every retrieved oocyte in the LE GnRH-ant group (β 0.05 ng/mL [95% CI 0.04, 0.06], < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-a group (β 0.02 ng/mL [95% CI 0.01, 0.03], < 0.001), with for interaction being 0.0002. LE supplementation on the antagonist protocols may increase progesterone levels in the late follicular stage.
Topics: Dietary Supplements; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Letrozole; Ovulation Induction; Progesterone; Retrospective Studies; Sperm Injections, Intracytoplasmic
PubMed: 35957830
DOI: 10.3389/fendo.2022.904089 -
The Cochrane Database of Systematic... Jul 2017Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
OBJECTIVES
To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.
SEARCH METHODS
We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
MAIN RESULTS
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis.
AUTHORS' CONCLUSIONS
Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Topics: Danazol; Dysmenorrhea; Dyspareunia; Endometriosis; Estrenes; Female; Gestrinone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Mifepristone; Norpregnadienes; Oximes; Prevalence; Randomized Controlled Trials as Topic; Receptors, Progesterone
PubMed: 28742263
DOI: 10.1002/14651858.CD009881.pub2 -
Steroids Jun 2022The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable...
The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable contraceptive Depo-MPA (DMPA), has off-target effects via the GR, which may result in side-effects in endocrine therapy. However, very little is known about the GR activity of other progestins used in endocrine therapy. This study compared GR activities for several progestins, using whole cell binding, dose-response, and GR phosphorylation assays, in both a cell line model and peripheral blood mononuclear cells (PBMCs). MPA, etonogestrel (ETG) and nestorone (NES) exhibit greater relative binding affinities for the GR than levonorgestrel (LNG) and norethisterone/norethindrone (NET) and are partial GR agonists for transactivation but agonists for transrepression on synthetic promoters in COS-1 cells. MPA is a potent agonist for endogenous GR-regulated GILZ and IL6 genes in PBMCs. While ETG and NES also display agonist activity on IL6, they have little effect on GILZ. In contrast, LNG and NET exhibit little to no activity in transactivation models, while both exhibit some transrepressive activity but are generally less potent and/or efficacious than MPA. Antagonist and phosphorylation assays confirmed that MPA and NES act via the GR on endogenous genes in PBMCs. Our results suggest GR-mediated dose-dependent and gene-specific transcriptional side-effects are likely to occur at physiologically relevant concentrations in vivo for MPA, may possibly occur selectively for ETG and NES, but are unlikely to occur for LNG and NET. This suggests that these progestins will exhibit differential side-effects in endocrine therapy via the GR.
Topics: Animals; COS Cells; Chlorocebus aethiops; Glucocorticoids; Interleukin-6; Leukocytes, Mononuclear; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Progestins; Receptors, Glucocorticoid
PubMed: 35271867
DOI: 10.1016/j.steroids.2022.108998 -
American Journal of Physiology. Heart... Aug 2020Progesterone exerts antihypertensive actions partially by modulating endothelial nitric oxide synthase (eNOS) activity. Here, we aimed to investigate the effects and...
Progesterone exerts antihypertensive actions partially by modulating endothelial nitric oxide synthase (eNOS) activity. Here, we aimed to investigate the effects and mechanisms of progesterone on eNOS expression. First, human umbilical vein endothelial cells (HUVECs) were exposed to progesterone and then the eNOS transcription factor specificity protein-1 (SP-1) and progesterone receptor (PR) expression were assessed by Western blotting and qRT-PCR. The interaction between SP-1 and PR was next determined through coimmunoprecipitation assay. The chromatin immunoprecipitation assay and luciferase assay were used to investigate the relationship of PR, SP-1, and eNOS promoter. At last, rats were intraperitoneally injected with progesterone receptor antagonist RU-486, and then the expression of eNOS and vasodilation function in thoracic aorta and mesenteric artery were measured. The results showed that progesterone could increase eNOS expression in HUVECs. Further study showed that progesterone increased PR-SP-1 complex formation and facilitated PR and SP-1 binding to eNOS promoter. Mutating SP-1 or PR-binding motif on eNOS promoter abolished the effect of progesterone on eNOS gene transcription. We also observed that progesterone receptor antagonist RU-486 reduced eNOS expression and impaired vasodilation in rats. Those results suggest that progesterone modulates eNOS expression through promoting PR-SP-1 complex formation, and progesterone antagonist attenuates eNOS expression, leading to the loss of vascular relaxation. Progesterone directly upregulated endothelial nitric oxide synthase (eNOS) expression in human endothelial cells. Progesterone augmented eNOS promoter activity through a progesterone receptor A- and specificity protein-1-dependent manner. Antagonism of the progesterone receptor reduced eNOS expression and impaired vasodilation in rats.
Topics: Animals; Aorta, Thoracic; Binding Sites; Cell Nucleus; Cells, Cultured; Enzyme Induction; Female; Hormone Antagonists; Human Umbilical Vein Endothelial Cells; Humans; Mesenteric Arteries; Nitric Oxide Synthase Type III; Progesterone; Promoter Regions, Genetic; Rats, Sprague-Dawley; Receptors, Progesterone; Signal Transduction; Sp1 Transcription Factor; Vasodilation
PubMed: 32618512
DOI: 10.1152/ajpheart.00206.2020 -
Journal of Natural Products Jan 2022Baicalein is a flavonoid extracted from the root of (Chinese skullcap) and is consumed as part of this botanical dietary supplement to reduce oxidative stress, pain,...
Baicalein is a flavonoid extracted from the root of (Chinese skullcap) and is consumed as part of this botanical dietary supplement to reduce oxidative stress, pain, and inflammation. We previously reported that baicalein can also modify receptor signaling through the progesterone receptor (PR) and glucocorticoid receptor (GR) , which is interesting due to the well-established roles of both PR and GR in reducing inflammation. To understand the effects of baicalein on PR and GR signaling in the uterus, ovariectomized CD-1 mice were treated with DMSO, progesterone (P4), baicalein, P4 with baicalein, and P4 with RU486, a PR antagonist, for a week. The uteri were collected for histology and RNA sequencing. Our results showed that baicalein attenuated the antiproliferative effect of P4 on luminal epithelium as well as on the PR target genes HAND2 and ZBTB16. Baicalein did not change levels of PR or GR RNA or protein in the uterus. RNA sequencing data indicated that many transcripts significantly altered by baicalein were regulated in the opposite direction by P4. Similarly, a large portion of GO/KEGG terms and GSEA gene sets were altered in the opposite direction by baicalein as compared to P4 treatment. Treatment of baicalein did not change body weight, organ weight, or blood glucose level. In summary, baicalein functioned as a PR antagonist and therefore may oppose P4 action under certain conditions such as uterine hyperplasia, fibroids, and uterine cancers.
Topics: Animals; Female; Flavanones; Gene Expression Regulation; Mice; Ovariectomy; Progesterone; Receptors, Glucocorticoid; Receptors, Progesterone; Sequence Analysis, RNA; Uterus
PubMed: 34935393
DOI: 10.1021/acs.jnatprod.1c01008 -
International Journal of Molecular... Jun 2022Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are...
Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student's -test or one-way ANOVA of GraphPad Prism and further compared by using the Student-Newman-Keuls test. Correlation analysis was also carried out using the CORR procedure of SAS to study the relationship between PMSs and BA levels in both maternal and fetal serum at G60, G90, and L0. Allopregnanolone sulphate (PM4S) and epiallopregnanolone sulphate (PM5S) were firstly identified in the maternal and fetal peripheral blood of pregnant sows by using newly developed ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Correlation analysis showed that pregnancy-associated maternal BA homeostasis was correlated with maternal serum PM4S levels, whereas fetal BA homeostasis was correlated with fetal serum PM5S levels. The antagonist activity role of PM5S on farnesoid X receptor (FXR)-mediated BA homeostasis and fibroblast growth factor 19 (FGF19) were confirmed in the PM5S and FXR activator co-treated pig primary hepatocytes model, and the antagonist role of PM4S on FXR-mediated BA homeostasis and FGF19 were also identified in the PM4S-treated pig primary hepatocytes model. Together with the high relative expression of in pig hepatocytes, the pregnant sow is a promising animal model to investigate the pathogenesis of cholestasis during pregnancy.
Topics: Animals; Female; Pregnancy; Bile Acids and Salts; Chromatography, Liquid; Fetus; Homeostasis; Liver; Progesterone; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Sulfates; Swine; Tandem Mass Spectrometry
PubMed: 35742938
DOI: 10.3390/ijms23126496 -
Breast Cancer Research and Treatment Aug 2020The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses are frequently discordant between the primary tumor...
BACKGROUND
The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses are frequently discordant between the primary tumor and metastatic lesions in metastatic breast cancer. This can have important therapeutic implications.
PATIENTS AND METHODS
In all, 541 patients with available receptor statuses from both primary tumor and metastatic lesion treated at Heidelberg and Tuebingen University Hospitals between 1982 and 2018 were included.
RESULTS
Statistically significant discordance rates of 14% and 32% were found for ER and PR. HER2 status was statistically insignificantly discordant in 15% of patients. Gain in HER2 positivity was associated with an improved overall survival, whereas loss of HR positivity was associated with worse overall survival. Antiendocrine treatment differed in 20% of cases before and after biopsy and HER2-directed treatment in 14% of cases.
CONCLUSIONS
Receptor statuses are discordant between primary tumor and metastasis in a considerable fraction of patients with metastatic breast cancer. Next to a highly presumed predictive value with respect to efficacy of endocrine and HER2-targeted therapy, discordance seems to provide prognostically relevant information. Where feasible, metastatic lesions should be biopsied in accordance with current guidelines.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Breast Neoplasms; Estrogens; Female; Follow-Up Studies; Germany; Humans; Kaplan-Meier Estimate; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Progesterone; Protein Kinase Inhibitors; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Young Adult
PubMed: 32613540
DOI: 10.1007/s10549-020-05746-8 -
Psychoneuroendocrinology Sep 2020This study assessed sex differences and the role of ovarian hormones in nicotine withdrawal. Study 1 compared physical signs, anxiety-like behavior, and corticosterone...
This study assessed sex differences and the role of ovarian hormones in nicotine withdrawal. Study 1 compared physical signs, anxiety-like behavior, and corticosterone levels in male, intact female, and ovariectomized (OVX) female rats during nicotine withdrawal. Estradiol (E2) and progesterone levels were also assessed in intact females that were tested during different phases of the 4-day estrous cycle. Study 2 assessed the role of ovarian hormones in withdrawal by comparing the same measures in OVX rats that received vehicle, E2, or E2+progesterone prior to testing. Briefly, rats received a sham surgery or an ovariectomy procedure. Fifteen days later, rats were prepared with a pump that delivered nicotine for 14 days. On the test day, rats received saline or the nicotinic receptor antagonist, mecamylamine to precipitate withdrawal. Physical signs and anxiety-like behavior were assessed on the elevated plus maze (EPM) and light-dark transfer (LDT) tests. During withdrawal, intact females displayed greater anxiety-like behavior and increases in corticosterone levels as compared to male and OVX rats. Females tested in the estrus phase (when E2 is relatively low) displayed less anxiety-like behavior and had lower corticosterone levels versus all other phases. Anxiety-like behavior and corticosterone levels were positively correlated with E2 and negatively correlated with progesterone levels. Intact females displaying high E2/low progesterone showed greater anxiety-like behavior and corticosterone levels as compared to females displaying low E2/high progesterone. Lastly, OVX-E2 rats displayed greater anxiety-like behavior than OVX-E2+progesterone rats. These data suggest that E2 promotes and progesterone reduces anxiety-like behavior produced by nicotine withdrawal.
Topics: Animals; Anxiety; Behavior, Animal; Estradiol; Female; Male; Nicotine; Ovariectomy; Progesterone; Rats; Rats, Wistar; Sex Characteristics; Substance Withdrawal Syndrome
PubMed: 32540678
DOI: 10.1016/j.psyneuen.2020.104694 -
Cancer Treatment Reviews Jun 2018Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast... (Review)
Review
Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched [HER2-E] and Basal-like) have been identified and intensively studied. In this article, we review and discuss the clinical implications of the 2 non-luminal subtypes (i.e. HER2-E and Basal-like) identified within hormone receptor (HR)-positive disease. After reviewing 32 studies for a total of 13,091 samples, ∼8% and ∼ 15% of early and metastatic HR+/HER2-negative breast cancer, respectively, were found to be non-luminal. Clinically, HR+/HER2-negative/non-luminal subtypes have been associated with estrogen independence, chemo-sensitivity, resistance to CDK4/6 inhibition and poor outcome. Interestingly, EGFR/HER2 tyrosine kinase inhibition might be of value in the HR+/HER2-negative/HER2-E subtype. Finally, the HER2-E subtype within HR+/HER2 + disease represents ∼ 30% and has been associated with anti-HER2 sensitivity, chemo-sensitivity and resistance to CDK4/6 inhibition. In the upcoming years, retrospective and prospective clinical trials evaluating both biomarkers should lead to improvements in patient outcomes.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Resistance, Neoplasm; Female; Humans; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 29763779
DOI: 10.1016/j.ctrv.2018.04.015 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9