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Contraception Feb 2017Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial... (Review)
Review
BACKGROUND
Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with nonuse. Few studies have examined whether nonoral formulations (including the combined hormonal patch, combined vaginal ring and combined injectable contraceptives) increase the risk of thrombosis compared with combined oral contraceptives (COCs).
OBJECTIVES
The objectives were to examine the risk of VTE and ATE among women using nonoral CHCs compared to women using COCs.
METHODS
We searched the PubMed database for all English language articles published from database inception through May 2016. We included primary research studies that examined women using the patch, ring or combined injectables compared with women using levonorgestrel-containing or norgestimate-containing COCs. Outcomes of interest included VTE (deep venous thrombosis or pulmonary embolism) or ATE (acute myocardial infarction or ischemic stroke). We assessed the quality of each individual piece of evidence using the system developed by the United States Preventive Services Task Force.
RESULTS
Eight studies were identified that met inclusion criteria. Of seven analyses from six studies examining VTE among patch users compared with levonorgestrel- or norgestimate-containing COC users, two found a statistically significantly elevated risk among patch users (risk estimates 2.2-2.3), one found an elevated risk that did not meet statistical significance (risk estimate 2.0), and four found no increased risk. Of three studies examining VTE among ring users compared with levonorgestrel COC users, one found a statistically significantly elevated risk among patch users (risk estimate 1.9) and two did not. Two studies did not find an increased risk for ATE among women using the patch compared with norgestimate COCs. We did not identify any studies examining combined injectable contraceptives.
CONCLUSION
Limited Level II-2 good to fair evidence demonstrated conflicting results on whether women using the patch or the ring have a higher risk of VTE than women using COCs. Evidence did not demonstrate an increased risk of ATE among women using the patch. Overall, any potential elevated risk likely represents a small number of events on a population level. Additional studies with standard methodology are needed to further clarify any associations and better understand mechanisms of hormone-induced thrombosis among users of nonoral combined hormonal contraception.
Topics: Administration, Cutaneous; Adolescent; Adult; Contraceptive Devices, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Estrogens; Female; Humans; Levonorgestrel; Norgestrel; Progestins; Risk Factors; Thromboembolism; Venous Thromboembolism; Young Adult
PubMed: 27771476
DOI: 10.1016/j.contraception.2016.10.005 -
Steroids Feb 2017The mortality of lung cancer presents a significant difference between the sexes. A role of hormone therapy (HT) in lung cancer mortality has been suggested, but the... (Meta-Analysis)
Meta-Analysis Review
The mortality of lung cancer presents a significant difference between the sexes. A role of hormone therapy (HT) in lung cancer mortality has been suggested, but the evidence is inconclusive. We sought to elucidate this issue with a meta-analysis. We conducted a systematic literature search in both Pubmed and Embase. Studies that reported the association of HT and mortality of lung cancer cases were included. Pooled hazard ratio (HR) was computed as the effect size to reflect the association between HT and lung cancer mortality. In total, 11 studies were included in the meta-analysis. The pooled HR of HT in relation to lung cancer mortality was 0.97 (95% CI 0.83-1.12, I=59.2%, p=0.006) in all studies disregarding study design, and it was 0.80 (95% CI: 0.69-0.92, I=21.4%, p=0.278) in prospective cohort studies. Results of this meta-analysis were robust, and there was no indication of significant differences in association in small and large studies. We observed a protective role of HT use in lung cancer mortality in pooled prospective cohorts, but not in pooled retrospective cohorts and post hoc analyses of randomized controlled trials. Future studies that address smoking, type and time of HT, menopausal status, and histology are warranted.
Topics: Estrogen Replacement Therapy; Estrogens; Female; Humans; Lung Neoplasms; Progestins; Prognosis
PubMed: 27964943
DOI: 10.1016/j.steroids.2016.12.005 -
Frontiers in Neuroendocrinology Apr 2023In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter...
In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.
Topics: Animals; Humans; Progestins; Progesterone; Contraceptive Agents; Cross-Sectional Studies; Progesterone Congeners; Brain
PubMed: 36758768
DOI: 10.1016/j.yfrne.2023.101060 -
The Journal of Sexual Medicine Dec 2022Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual... (Review)
Review
Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning; A Systematic Literature Review.
BACKGROUND
Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual symptoms.
AIMS
To systematically review and meta-analyze the effect of systemic hormone replacement therapy (sHRT) on psychological well-being and sexual functioning in women after surgical menopause and BSO.
METHODS
Medline/Pubmed, EMBASE and PsychInfo were systematically searched until November 2021. Randomized controlled trials investigating the effect of sHRT on psychological well-being and/or sexual functioning in surgically menopausal women and women after BSO were eligible for inclusion. Two independent authors performed study selection, risk of bias assessment and data extraction. Standardized mean differences (SMDs) were calculated.
OUTCOMES
Primary outcomes for psychological well-being were defined as overall psychological well-being, depression, and anxiety. Primary outcomes for sexual functioning were defined as overall sexual functioning, sexual desire, and sexual satisfaction. All outcomes were assessed on short (≤12 weeks) or medium term (13-26 weeks).
RESULTS
Twelve studies were included. Estradiol had a beneficial effect on depressed mood on short term 3-6 years after surgery or 2 years (median) after surgery with high heterogeneity (SMD: -1.37, 95%CI: -2.38 to -0.37, P = .007, I 79%). Testosterone had a beneficial effect on overall sexual functioning on short to medium term 4.6 years (mean) after surgery (SMD 0.38, 95%CI 0.11-0.65, I 0%) and on sexual desire on medium term at least 3-12 months after surgery (SMD 0.38, 95%CI 0.19-0.56, I 54%). For most studies, risk of bias was uncertain.
CLINICAL IMPLICATIONS
Estradiol may beneficially affect psychological symptoms after surgical menopause or BSO and testosterone might improve sexual desire and overall sexual functioning.
STRENGTHS AND LIMITATIONS
This review only included patient-reported outcomes, thereby reflected perceived and not simply objective symptoms in surgically menopausal women and women after BSO. The small number of studies highly varied in nature and bias could not be excluded, therefore our results should be interpreted with great caution.
CONCLUSION
Independent randomized controlled clinical trials investigating the effects of estrogen-progesterone and testosterone on psychological and sexual symptoms after surgical menopause are needed.
PROSPERO REGISTRATION NUMBER
CRD42019136698. Stuursma A, Lanjouw L, Idema DL, et al. Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning: A Systematic Literature Review. J Sex Med 2022;19:1778-1789.
Topics: Humans; Female; Progesterone; Quality of Life; Hormone Replacement Therapy; Menopause; Ovariectomy; Estrogens; Testosterone; Estradiol
PubMed: 36175351
DOI: 10.1016/j.jsxm.2022.08.191 -
Current Medical Research and Opinion Mar 2022The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms...
OBJECTIVE
The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms and quality of life.
METHODS
A literature search of PubMed, Ovid (MEDLINE and EMBASE), and Web of Science was performed from inception to December 2020. In addition, a targeted search of cited references was also performed. Our search identified 330 articles of which 17 were deemed eligible for full-text review. Eligible studies included randomized control trials, observational studies, and case series with at least 5 cases, investigating the effect of progestin subdermal implants on endometriosis-related pain scores in women of reproductive age with a clinical, radiologic, or surgical diagnosis of endometriosis. Six articles were excluded after the full-text screen.
RESULTS
Eleven articles describing a total of 335 patients were eligible for inclusion. Across all studies, etonogestrel- and segesterone-releasing progestin subdermal implants improved VAS pain scores for cyclic pelvic pain/dysmenorrhea (VAS at baseline ranged from 6.1 to 7.5 cm and after treatment from 1.7 to 4.9 cm, = 121), non-cyclic pelvic pain (baseline VAS 7.2-7.6 cm and after treatment 2.0-3.7 cm, = 96) and dyspareunia (baseline VAS 1.61-8.3 cm and after treatment 1.0-7.1 cm, = 87). Symptom improvement with the progestin subdermal implant was equivalent to treatment with depot medroxyprogesterone acetate (DMPA; average baseline VAS 6.5 and after DMPA treatment 3.0, compared to 2.0 after treatment with the implant) or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS; baseline cyclic and non-cyclic pain scores 7.3 and 7.4 respectively decreased to 1.9 and 1.9 after LNG-IUS treatment). Improvements were also demonstrated in quality-of-life scores (average improvement of 36% in all domains of the Endometriosis Health Profile-30 and significant improvements in social functioning, general health, bodily pain, vitality and mental health domains on the Short Form-36 questionnaire) and sexual function (total sexual function score improved from 24 to 25.35 and 26.25 at 6 and 12 months).
CONCLUSION
Etonogestrel- and segesterone-releasing progestin subdermal implants appear to improve endometriosis-related pain symptoms and quality of life and may provide an additional component in the management of endometriosis. However, this systematic review is limited by the small sample size and heterogeneity in the data. As such, larger prospective randomized trials are needed to guide further management.
PROSPERO REGISTRATION
CRD42021225665.
Topics: Endometriosis; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pelvic Pain; Progestins; Prospective Studies; Quality of Life
PubMed: 35048754
DOI: 10.1080/03007995.2022.2031144 -
BMC Women's Health Jan 2024Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for the cardiovascular system of postmenopausal women are not very clear.
OBJECTIVES
To evaluate cardiovascular benefits and risks of MHT in postmenopausal women, and analyze the underlying factors that affect both.
SEARCH STRATEGY
The EMBASE, MEDLINE, and CENTRAL databases were searched from 1975 to July 2022.
SELECTION CRITERIA
Randomized Clinical Trials (RCTs) that met pre-specified inclusion criteria were included.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data independently. A meta-analysis of random effects was used to analyze data.
MAIN RESULTS
This systematic review identified 33 RCTs using MHT involving 44,639 postmenopausal women with a mean age of 60.3 (range 48 to 72 years). There was no significant difference between MHT and placebo (or no treatment) in all-cause death (RR = 0.96, 95%CI 0.85 to 1.09, I = 14%) and cardiovascular events (RR = 0.97, 95%CI 0.82 to 1.14, I = 38%) in the overall population of postmenopausal women. However, MHT would increase the risk of stroke (RR = 1.23, 95%CI 1.08 to 1.41,I = 0%) and venous thromboembolism (RR = 1.86, 95%CI 1.39 to 2.50, I = 24%). Compared with placebo, MHT could improve flow-mediated arterial dilation (FMD) (SMD = 1.46, 95%CI 0.86 to 2.07, I = 90%), but it did not improve nitroglycerin-mediated arterial dilation (NMD) (SMD = 0.27, 95%CI - 0.08 to 0.62, I = 76%). Compared with women started MHT more than 10 years after menopause, women started MHT within 10 years after menopause had lower frequency of all-cause death (P = 0.02) and cardiovascular events (P = 0.002), and more significant improvement in FMD (P = 0.0003). Compared to mono-estrogen therapy, the combination therapy of estrogen and progesterone would not alter the outcomes of endpoint event. (all-cause death P = 0.52, cardiovascular events P = 0.90, stroke P = 0.85, venous thromboembolism P = 0.33, FMD P = 0.46, NMD P = 0.27).
CONCLUSIONS
MHT improves flow-mediated arterial dilation (FMD) but fails to lower the risk of all-cause death and cardiovascular events, and increases the risk of stroke and venous thrombosis in postmenopausal women. Early acceptance of MHT not only reduces the risk of all-cause death and cardiovascular events but also further improves FMD, although the risk of stroke and venous thrombosis is not reduced. There is no difference in the outcome of cardiovascular system endpoints between mono-estrogen therapy and combination therapy of estrogen and progesterone.
Topics: Female; Humans; Middle Aged; Aged; Venous Thromboembolism; Postmenopause; Progesterone; Arteries; Stroke; Estrogens; Hormone Replacement Therapy; Venous Thrombosis; Risk Assessment
PubMed: 38263123
DOI: 10.1186/s12905-023-02788-0 -
Maturitas Mar 2010Lung cancer rates increase among women in many regions of the world. To explore whether menopausal hormone therapy (MHT) plays a role. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Lung cancer rates increase among women in many regions of the world. To explore whether menopausal hormone therapy (MHT) plays a role.
METHODS
We conducted a systematic search of the literature and performed meta-analyses of cohort studies (C), case-control studies (CC), randomized controlled trials (RCTs), and cancer registry studies (CR) to analyse the impact of estrogen therapy (ET), estrogen/progestin therapy (EPT) and any hormone therapy (HT) on lung cancer risks. We explored associations between ever-use of therapies and risks, analysed annual changes of risk, and the impact of therapies on histological subtypes. We calculated summary odds ratios, relative risks, 95% confidence intervals (CI; fixed-effects model), and assessed heterogeneity across studies. Eighteen studies were eligible (9 CC, 4 C, 3 RCT, 2 CR).
RESULTS
We found a significant increase of risk - 76.2% - in non-smoking women with adenocarcinoma (CI 1.072-2.898) reporting ever-use of HT. Estrogen plus progestin therapy does not change the risk; however, the pooled analysis of 2 RCTs points at an increased risk (RR 1.359; CI 1.031-1.791). Our further results should be interpreted with caution as significances were found in analyses only when smoking and non-smoking women, various hormone regimens, or histological subtypes, respectively, were pooled.
CONCLUSIONS
Dedicated studies designed to more adequately delineate the role of MHT are necessary to substantiate whether use of MHT is a risk factor for this or other types of lung cancer.
Topics: Adenocarcinoma; Estrogen Replacement Therapy; Female; Humans; Lung Neoplasms; Menopause; Odds Ratio; Risk Factors; Smoking
PubMed: 20031346
DOI: 10.1016/j.maturitas.2009.11.027 -
Frontiers in Neuroendocrinology Oct 2023Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females,... (Review)
Review
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.
Topics: Female; Humans; Male; Dopamine; Epigenesis, Genetic; Gonadal Steroid Hormones; Meta-Analysis as Topic; Progesterone; Sex Characteristics; Substance-Related Disorders; Systematic Reviews as Topic; Testosterone
PubMed: 37543184
DOI: 10.1016/j.yfrne.2023.101085 -
Advances in Therapy Nov 2022Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.
METHODS
We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).
RESULTS
We identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic.
CONCLUSIONS
We confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.
Topics: Dysmenorrhea; Estrogens; Female; Gastrointestinal Diseases; Humans; Japan; Network Meta-Analysis; Norethindrone; Progestins
PubMed: 36048405
DOI: 10.1007/s12325-022-02298-9 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Male; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49