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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 -
Minerva Obstetrics and Gynecology Dec 2023Despite the many unknowns about its exact mechanism, progesterone and progestins are being successfully used to prevent luteinizing hormone (LH) surge during ovarian... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Despite the many unknowns about its exact mechanism, progesterone and progestins are being successfully used to prevent luteinizing hormone (LH) surge during ovarian stimulation for assisted reproductive technology (ART). We will review progestin primed ovarian stimulation (PPOS) protocols in comparison with gonadotropin releasing hormone (GnRH) analogues and each other.
EVIDENCE ACQUISITION
MEDLINE via PubMed; Cochrane Central Register of Controlled Trials (CENTRAL); Scopus; Web of Science were screened with keywords related to assisted reproductive technology, ovarian stimulation progesterone, GnRH analogue and progesterone in several combinations. Search period was from the date of inception of each database until 20 May 2022.
EVIDENCE SYNTHESIS
Live birth or ongoing pregnancy rate per embryo transfer (ET) was similar in PPOS and GnRH antagonist cycles (RR=1.16, 95% CI: 0.93-1.44). Clinical pregnancy rate per ET was likewise similar (RR=1.12, 95% CI: 0.92-1.37). Miscarriage rate per pregnancy was similar with PPOS and GnRH antagonists in autologous cycles (RR=1.01, 95% CI: 0.65-1.55). Pooled analyses showed similar live birth rate between progestins and short GnRH agonist protocols (RR=1.01, 95% CI: 0.49-2.09), however, clinical pregnancy rates per ET were significantly higher with progestins (RR=1.31, 95% CI: 1.06-1.62). Miscarriage rate per pregnancy was similar with progestins (RR=0.82, 95% CI: 0.55-1.21).
CONCLUSIONS
Progestins seem to be an efficient option for pituitary suppression during ovarian suppression, providing similar outcomes for stimulation and pregnancy. They can be especially beneficial for women for whom fresh ET is not considered.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovulation Induction; Progesterone; Progestins
PubMed: 36193835
DOI: 10.23736/S2724-606X.22.05176-4 -
The Cochrane Database of Systematic... Jul 2009The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to antagonise the action of progesterone, and have a recognised role in medical termination of early or mid-trimester pregnancy. Animal studies have suggested that mifepristone may also have a role in inducing labour in late pregnancy.
OBJECTIVES
To determine the effects of mifepristone for third trimester cervical ripening or induction of labour.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and reference lists of relevant papers (May 2009).
SELECTION CRITERIA
Clinical trials comparing mifepristone used for third trimester cervical ripening or labour induction with placebo/no treatment or other labour induction methods.
DATA COLLECTION AND ANALYSIS
A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. For this update, two review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Ten trials (1108 women) are included. Compared to placebo, mifepristone treated women were more likely to be in labour or to have a favourable cervix at 48 hours (risk ratio (RR) 2.41, 95% confidence intervals (CI) 1.70 to 3.42) and this effect persisted at 96 hours (RR 3.40, 95% CI 1.96 to 5.92). They were less likely to need augmentation with oxytocin (RR 0.80, 95% CI 0.66 to 0.97). Mifepristone treated women were less likely to undergo caesarean section (RR 0.74, 95% CI 0.60 to 0.92) but more likely to have an instrumental delivery (RR 1.43, 95% CI 1.04 to 1.96). Women receiving mifepristone were less likely to undergo a caesarean section as a result of failure to induce labour (RR 0.40, 95% CI 0.20 to 0.80). There is insufficient evidence to support a particular dose but a single dose of 200 mg mifepristone appears to be the lowest effective dose for cervical ripening (increased likelihood of cervical ripening at 72 hours (RR 2.13, 95% CI 1.15 to 3.97). Abnormal fetal heart rate patterns were more common after mifepristone treatment (RR 1.85, 95% CI 1.17 to 2.93), but there was no evidence of differences in other neonatal outcomes. There is insufficient information on the occurrence of uterine rupture/dehiscence in the reviewed studies.
AUTHORS' CONCLUSIONS
There is insufficient information available from clinical trials to support the use of mifepristone to induce labour. However, the studies suggest that mifepristone is better than placebo in reducing the likelihood of caesarean sections being performed for failed induction of labour; therefore, this may justify future trials comparing mifepristone with the routine cervical ripening agents currently in use. There is little information on effects on the baby.
Topics: Female; Humans; Labor Stage, First; Labor, Induced; Mifepristone; Oxytocics; Pregnancy; Progesterone; Randomized Controlled Trials as Topic
PubMed: 19588336
DOI: 10.1002/14651858.CD002865.pub2 -
The Cochrane Database of Systematic... Aug 2012Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials.
OBJECTIVES
To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre-menopausal women.
SEARCH METHODS
We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions.
SELECTION CRITERIA
Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre-menopausal women with confirmed uterine fibroids were included.
DATA COLLECTION AND ANALYSIS
Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta-analyses were performed using the fixed-effect model.
MAIN RESULTS
Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I(2) = 0%). Three studies (Bagaria 2009; Engman 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) -0.02; 95% CI -0.38 to 0.41; 99 women). Two studies (Bagaria 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) -77.24; 95% CI -240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I(2) = 0%). Only one study (Bagaria 2009) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study (Fiscella 2006) suggested significant improvements (P < 0.001) for specific quality of life outcomes.
AUTHORS' CONCLUSIONS
Mifepristone reduced heavy menstrual bleeding and improved fibroid-specific quality of life. However, it was not found to reduce fibroid volume. Further well-designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids.
Topics: Female; Humans; Leiomyoma; Menorrhagia; Mifepristone; Premenopause; Randomized Controlled Trials as Topic; Receptors, Progesterone; Tumor Burden; Uterine Neoplasms
PubMed: 22895965
DOI: 10.1002/14651858.CD007687.pub2 -
Annals of Oncology : Official Journal... Sep 2012Triple-negative breast cancer (TNBC) is a distinct subset of breast cancer (BC) defined by the lack of immunohistochemical expression of the estrogen and progesterone... (Review)
Review
BACKGROUND
Triple-negative breast cancer (TNBC) is a distinct subset of breast cancer (BC) defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. It is highly heterogeneous and displays overlapping characteristics with both basal-like and BC susceptibility gene 1 and 2 mutant BCs. This review evaluates the activity of emerging targeted agents in TNBC.
DESIGN
A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with targeted and platinum-based therapies.
RESULTS AND DISCUSSION
Our review identified TNBC studies of agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. Combining targeted agents with chemotherapy in TNBC produced only modest gains in progression-free survival, and had little impact on survival. Six TNBC subgroups have been identified and found to differentially respond to specific targeted agents. The use of biological preselection to guide therapy will improve therapeutic indices in target-bearing populations.
CONCLUSION
Ongoing clinical trials of targeted agents in unselected TNBC populations have yet to produce substantial improvements in outcomes, and advancements will depend on their development in target-selected populations.
Topics: Antineoplastic Agents; Breast Neoplasms; ErbB Receptors; Female; Humans; Molecular Targeted Therapy; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 22517820
DOI: 10.1093/annonc/mds067 -
Annals of the New York Academy of... Nov 2006Animal models of experimental liver carcinogenesis and epidemiological studies in humans suggest a relationship between sex hormones and hepatocellular carcinoma (HCC).... (Review)
Review
Animal models of experimental liver carcinogenesis and epidemiological studies in humans suggest a relationship between sex hormones and hepatocellular carcinoma (HCC). In 1997, a systematic review of the existing, small randomized trials evaluating the antiestrogen tamoxifen yielded a positive result, but the large randomized CLIP-1 trial showed no survival advantage from the addition of tamoxifen to best supportive care. A possible explanation for the negative results is the lack of patient selection, but the expression of estrogen (ER) and progesterone (PgR) receptors in HCC does not clearly affect the survival outcome of the patients treated with tamoxifen. In the last years, it has been proposed that negative results might be due to the fact that tamoxifen in HCC could act via an ER-independent pathway, which requires much higher doses than those usually administered, but a double-blind Asian randomized trial conducted to assess possible dose-response effect showed no efficacy for tamoxifen, with an inversely negative impact with increasing dose. According to the results of large trials and of the Cochrane systematic review, neither further trials are warranted with tamoxifen in HCC, nor should any use in clinical practice be considered. Interesting results have been obtained when the type of hormonal treatment (tamoxifen or megestrol) has been chosen according to the presence of wild-type or variant ER, but these results should be confirmed in large randomized trials. Negative results have been obtained with antiandrogen therapy. In conclusion, hormonal treatment should not be a part of the current management of HCC patients.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Estrogen Antagonists; Humans; Liver Neoplasms; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Treatment Failure; Treatment Outcome
PubMed: 17261772
DOI: 10.1196/annals.1386.007 -
The Cochrane Database of Systematic... Jul 2007Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women.
OBJECTIVES
To determine the effectiveness and tolerability of Danazol when used for heavy menstrual bleeding in women of reproductive years.
SEARCH STRATEGY
We searched the Menstrual Disorders and Subfertility Group's Specialised Register (April 2007). We also searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2007), MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007, CINAHL (1982 to April 2007). Attempts were also made to identify trials from citation lists of included trials and relevant review articles.
SELECTION CRITERIA
Randomised controlled trials of Danazol versus placebo, any other medical (non-surgical) therapy or Danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded.
DATA COLLECTION AND ANALYSIS
Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format.
MAIN RESULTS
Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with Danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7 to 28.2) and progestogens (OR 4.05, 95% CI 1.6 to10.2). Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8 to -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3 to -4.8). There were no randomised trials comparing Danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system.
AUTHORS' CONCLUSIONS
Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified.
Topics: Danazol; Estrogen Antagonists; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 17636649
DOI: 10.1002/14651858.CD001017.pub2 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
European Journal of Obstetrics,... Jul 2017Ulipristal acetate is increasingly used for several clinical indications, like emergency contraception and pre-treatment of uterine fibroids. It has mixed progesterone... (Review)
Review
Ulipristal acetate is increasingly used for several clinical indications, like emergency contraception and pre-treatment of uterine fibroids. It has mixed progesterone agonist and antagonist effects in the myometrium and endometrium. Due to its progesterone antagonistic effect, an unopposed estrogen effect could occur which could cause (pre-)malignant lesions in the endometrium. Several studies have been performed to evaluate this possible increased risk for endometrial malignancies when using ulipristal acetate. The specific spectrum of morphological changes due to ulipristal acetate, named progesterone receptor modulator associated endometrial changes (PAEC), occurs to be reversible after discontinuing ulipristal acetate. In this systematic review we provide a detailed overview of the literature on histopathological endometrial changes and imaging characteristics of the endometrium in ulipristal acetate users. We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed in accordance with the prisma guidelines. All studies published as full papers in peer reviewed journals using ulipristal acetate reporting on endometrial changes were included, independent of clinical indication, dosage taken and duration of therapy. No language restrictions were applied. Ten studies with a total of 1450 participants were included. Seven were randomized clinical trials and three prospective cohort studies. A quality assessment of all included studies was performed. In only five of ten studies an endometrial biopsy was performed during treatment. All of these studies described specific histological non-physiological endometrial changes (PAEC) due to ulipristal acetate, varying from 41 to 78.8% of all patients. Three of these studies also performed follow-up biopsies after discontinuing ulipristal acetate. The percentage of PAEC decreased from 62% to 0%, 78.8% to 0% and from 59% to 6-7% after the treatment period. In six of 1450 women (0.4%) endometrial hyperplasia was reported during or after ulipristal acetate use. Five were simple hyperplasia, one biopsy showed simple atypical endometrial hyperplasia that resolved into benign secretory endometrium by the end of the treatment. One case of endometrial adenocarcinoma was reported, however this does not seem to be related to ulipristal acetate use, since it was already present at the baseline biopsy. In eight of ten studies a transvaginal ultrasound or MRI was performed at any moment to assess the endometrial thickness before, during and after treatment. Most studies showed a transient increase of endometrial thickness during treatment, which returned to normal within a few weeks after discontinuing ulipristal acetate. Based on the literature found in this systematic review, follow-up after a maximum of four courses of ulipristal acetate did not report any non-reversible (pre-)malignant lesions of the endometrium. Most studies focused on short term use of ulipristal acetate and their follow-up period was limited. Therefore, we believe more information concerning long term (intermittent) use is needed before it can be concluded that its use is completely safe.
Topics: Contraceptive Agents, Female; Endometrium; Female; Humans; Leiomyoma; Norpregnadienes
PubMed: 28482329
DOI: 10.1016/j.ejogrb.2017.04.042 -
Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis.Gynecologic Oncology Oct 2017Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT. Here, we quantify its effects and explore the influence of clinico-pathologic factors and hormone receptor (HR) status on overall response rates (ORR).
METHODS
A systematic search of electronic databases identified publications of HT in advanced EC. Data from individual studies reporting ORR, median progression-free (PFS) or overall survival (OS) were weighted by individual study sample size and pooled in a meta-analysis. Outcomes of estrogen (ER) and progesterone receptor (PgR) subgroups were collected. Studies of first- and second-line HT were analyzed independently. Mixed studies were included if subgroup data based on previous HT exposure were provided. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on outcomes.
RESULTS
Thirty-nine studies were included, with seven providing subgroup data based on HR status. First-line HT was associated with a mean ORR of 21.6% and clinical benefit rate (CBR) of 36.7%. Median PFS and OS were 2.8 and 10.2months respectively. ORR was 20.4% in clinical trials and 25.3% in observational studies. Magnitude of ORR was lower in older age, adenosquamous histology and high grade. ORR was higher in ER+ (26.5%) and PgR+ (35.5%) disease, and lower in ER- (9.2%) or PgR- (12.1%) tumors. Second-line ORR was 18.5%. CBR was 35.8%, but was significantly associated with timing of stable disease assessments in first- and second-line. Meta-regression performed in mixed and second-line studies showed an association between previous HT and greater ORR (β 0.561; p=0.024), suggesting potential confounding by indication (re-treatment of good responders to first-line HT).
CONCLUSION
HT is associated with modest ORR in advanced EC, and is greatest in HR+ tumors. Response rates in second-line are likely dependent on response to previous HT.
Topics: Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Endometrial Neoplasms; Female; Gonadal Hormones; Hormone Antagonists; Humans; Selective Estrogen Receptor Modulators; Survival Analysis
PubMed: 28689667
DOI: 10.1016/j.ygyno.2017.07.002