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Systematic Reviews Jul 2016Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model.
RESULTS
We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81.
CONCLUSIONS
Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
Topics: Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Humans; Observational Studies as Topic; Progesterone; Progesterone Congeners; Progestins; Risk Factors
PubMed: 27456847
DOI: 10.1186/s13643-016-0294-5 -
Gynecologic Oncology May 2012The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical... (Review)
Review
OBJECTIVE
The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy.
METHODS
A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fisher's exact test was used to calculate statistical differences.
RESULTS
Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p=.002). The median time to complete response was 6 months (range, 1-18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p=.03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p=.02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p=.39), with 117 live births reported.
CONCLUSION
Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts.
Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Pregnancy; Pregnancy Outcome; Progestins; Treatment Outcome
PubMed: 22245711
DOI: 10.1016/j.ygyno.2012.01.003 -
Breast Cancer Research and Treatment Aug 2020Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic...
PURPOSE
Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD.
METHODS
Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy.
RESULTS
Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users.
CONCLUSIONS
Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.
Topics: Breast Density; Breast Neoplasms; Female; Hormone Replacement Therapy; Humans; Risk Factors
PubMed: 32572713
DOI: 10.1007/s10549-020-05744-w -
Gynecologic Oncology Apr 2012To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or... (Meta-Analysis)
Meta-Analysis Review
Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature.
OBJECTIVES
To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or early endometrial adenocarcinoma (EC).
METHODS
A systematic search identified 3245 potentially relevant citations. Studies containing less than ten eligible CAH or EC patients in either oral or intrauterine treatment arm were excluded. Only information from patients receiving six or more months of treatment and not receiving other treatments was included. Weighted proportions of patients achieving pCR were calculated using R software.
RESULTS
Twelve studies met the selection criteria. Eleven studies reported treatment of patients with oral (219 patients, 117 with CAH, 102 with grade 1 Stage I EC) and one reported treatment of patients with intrauterine progestin (11 patients with grade 1 Stage IEC). Overall, 74% (95% confidence interval [CI] 65-81%) of patients with CAH and 72% (95% CI 62-80%) of patients with grade 1 Stage I EC achieved a pCR to oral progestin. Disease progression whilst on oral treatment was reported for 6/219 (2.7%), and relapse after initial complete response for 32/159 (20.1%) patients. The weighted mean pCR rate of patients with grade 1 Stage I EC treated with intrauterine progestin from one prospective pilot study and an unpublished retrospective case series from the Queensland Centre of Gynaecologic Oncology (QCGC) was 68% (95% CI 45-86%).
CONCLUSIONS
There is a lack of high quality evidence for the efficacy of progestin in CAH or EC. The available evidence however suggests that treatment with oral or intrauterine progestin is similarly effective. The risk of progression during treatment is small but longer follow-up is required. Evidence from prospective controlled clinical trials is warranted to establish how the efficacy of progestin for the treatment of CAH and EC can be improved further.
Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Agents, Hormonal; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Humans; Intrauterine Devices, Medicated; Progestins; Treatment Outcome
PubMed: 22196499
DOI: 10.1016/j.ygyno.2011.11.043 -
Critical Reviews in Oncology/hematology Dec 2014Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive... (Meta-Analysis)
Meta-Analysis Review
Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias.
Topics: Contraception; Female; Hormone Replacement Therapy; Humans; Lymphoma, Non-Hodgkin; Male; Reproductive Physiological Phenomena; Risk Factors
PubMed: 25132165
DOI: 10.1016/j.critrevonc.2014.07.004 -
Climacteric : the Journal of the... Apr 2018Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including...
Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including micronized progesterone has increased in recent years. Based on a systematic literature review on the impact of menopausal hormone therapy (MHT) containing micronized progesterone on the mammary gland, an international expert panel's recommendations are as follows: (1) estrogens combined with oral (approved) or vaginal (off-label use) micronized progesterone do not increase breast cancer risk for up to 5 years of treatment duration; (2) there is limited evidence that estrogens combined with oral micronized progesterone applied for more than 5 years are associated with an increased breast cancer risk; and (3) counseling on combined MHT should cover breast cancer risk - regardless of the progestogen chosen. Yet, women should also be counseled on other modifiable and non-modifiable breast cancer risk factors in order to balance the impact of combined MHT on the breast.
Topics: Breast; Breast Neoplasms; Endometrium; Estrogen Replacement Therapy; Female; Humans; Menopause; Progesterone; Progestins; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 29384406
DOI: 10.1080/13697137.2017.1421925 -
Maturitas Sep 2016In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that... (Review)
Review
BACKGROUND
In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account.
AIM
This systematic literature review assesses the safety of estrogen plus progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin.
METHODS
PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio.
RESULTS
28 studies were included. The observational literature found an increased risk among users of estrogen alone. Continuous combined therapy showed a lower risk than sequential combined therapy. The newer marketed micronized progesterone increased the risk notably, also when administered continuously. In most studies, tibolone was associated with an increased risk.
CONCLUSION
Use of unopposed estrogen, tibolone and sequential combined therapy increases the risk of endometrial cancer. Continuous combined therapy seems risk free, but possibly not when micronized progesterone is used.
Topics: Endometrial Neoplasms; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Odds Ratio; Postmenopause; Practice Guidelines as Topic; Progestins; Risk Factors
PubMed: 27451318
DOI: 10.1016/j.maturitas.2016.05.013 -
Presse Medicale (Paris, France : 1983) Nov 2019Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an...
Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an important public health issue. In this perspective, we conducted a review of the risk of hypertension associated with the use of hormonal contraceptives, either combined estrogen-progestin or only progestin. The use of combined hormonal contraceptives, regardless of its type and route of administration, is associated with a slight increase in blood pressure, both systolic and diastolic blood pressures. The frequency of onset of hypertension in women who use combined hormonal contraception is between 0.6% and 8.5%. Progestin-only contraception seems safe with respect to the risk of hypertension. It is therefore important to remember that the use of combined hormonal contraception is contra-indicated in hypertensive women, even well controlled. Finally, we propose a prescription assistance algorithm according to the recommendations of an expert panel. It should be remembered that taking blood pressure at each contraceptive consultation (initial and follow-up) is essential.
Topics: Adolescent; Adult; Blood Pressure; Blood Pressure Determination; Contraception; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Hypertension; Middle Aged; Progestins; Risk Factors; Young Adult
PubMed: 31757732
DOI: 10.1016/j.lpm.2019.07.033 -
Journal of the National Cancer Institute Aug 2008Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.
METHODS
We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.
RESULTS
We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.
CONCLUSIONS
There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.
Topics: Anemia; Antidepressive Agents, Second-Generation; Antineoplastic Agents; Central Nervous System Stimulants; Darbepoetin alfa; Dopamine Uptake Inhibitors; Erythropoietin; Fatigue; Hematinics; Humans; Methylphenidate; Neoplasms; Odds Ratio; Paroxetine; Progestins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18695134
DOI: 10.1093/jnci/djn250 -
International Journal of Gynecological... Dec 2021Progestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Progestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.
METHODS
A systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.
RESULTS
In total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).
CONCLUSION
For reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.
PROSPERO REGISTRATION NUMBER
CRD42020179069.disease remission.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Metformin; Neoplasm Recurrence, Local; Pregnancy; Progestins
PubMed: 34785524
DOI: 10.1136/ijgc-2021-002699