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Cancer Journal (Sudbury, Mass.)Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative... (Review)
Review
Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the Women's Health Initiative's (2020) two randomized trials evaluating conjugated equine estrogen alone, for women with prior hysterectomy or with medroxyprogesterone acetate. Findings are generally concordant for estrogen plus progestin use with both observational and randomized studies reporting higher breast cancer incidence. Findings are discordant for estrogen-alone use where, in the WHI randomized trial, a lower incidence and lower breast cancer mortality was seen. In contrast, in the observational studies, estrogen-alone use was associated with higher breast cancer incidence and higher breast cancer mortality. Although these discordant findings are difficult to fully reconcile, we conclude with a discussion of public health implications of the available evidence on menopausal hormone therapy and breast cancer.
Topics: Breast Neoplasms; Estrogen Replacement Therapy; Estrogens; Female; Humans; Observational Studies as Topic; Postmenopause; Progestins; Randomized Controlled Trials as Topic
PubMed: 35594463
DOI: 10.1097/PPO.0000000000000601 -
Maturitas Sep 2022The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after... (Review)
Review
Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.
AIM
The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT).
MATERIALS AND METHODS
Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence.
SUMMARY RECOMMENDATIONS
The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).
Topics: Estrogen Replacement Therapy; Estrogens; Female; Humans; Menopause; Postmenopause; Practice Guidelines as Topic; Progestins
PubMed: 35717745
DOI: 10.1016/j.maturitas.2022.05.008 -
Best Practice & Research. Clinical... Sep 2022Rates of unplanned pregnancies are high globally, burdening women and families. Efforts to develop male contraceptive agents have been thwarted by unacceptable failure... (Review)
Review
Rates of unplanned pregnancies are high globally, burdening women and families. Efforts to develop male contraceptive agents have been thwarted by unacceptable failure rates, side effects and a dearth of pharmaceutical industry involvement. Hormonal male contraception consists of exogenous androgens which exert negative feedback on the hypothalamic-pituitary-gonadal axis and suppress gonadotropin production. This in turn suppresses testicular testosterone production and sperm maturation. Addition of a progestin suppresses spermatogenesis more effectively in men. Contraceptive efficacy studies in couples have shown male hormonal methods are effective and reversible, but also may come with side effects related to sexual desire, acne and serum cholesterol and inconvenient methods of dosing and delivery. Recently, novel androgens as potential contraceptive agents are being evaluated in early clinical trials and look to overcome these drawbacks. Here we summarize landmark studies of prototype male hormonal contraceptives, showcasing recent advances and future prospects in this important area of public health.
Topics: Androgens; Cholesterol; Contraception; Contraceptive Agents, Male; Female; Gonadotropins; Humans; Male; Pregnancy; Progestins; Semen; Spermatogenesis; Testosterone
PubMed: 35249804
DOI: 10.1016/j.beem.2022.101627 -
Frontiers in Endocrinology 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.
METHODS
We searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.
RESULTS
The clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, < 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, < 0.001, = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, < 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, < 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, < 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, < 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, < 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, = 0.01)].
CONCLUSION
The findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Infertility, Female; Live Birth; Ovarian Reserve; Ovulation Induction; Pregnancy Rate; Progestins; Randomized Controlled Trials as Topic
PubMed: 34531825
DOI: 10.3389/fendo.2021.702558 -
Ugeskrift For Laeger May 2024This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality... (Review)
Review
This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.
Topics: Humans; Premature Birth; Pregnancy; Progesterone; Female; Progestins; Administration, Intravaginal; Risk Factors; Cervical Length Measurement; Cervix Uteri
PubMed: 38847312
DOI: 10.61409/V10230636 -
Minerva Obstetrics and Gynecology Aug 2022In this paper, we report general pharmacological profile and major biological activities of natural progesterone (P) and progestins. The aim of this article consists of... (Review)
Review
INTRODUCTION
In this paper, we report general pharmacological profile and major biological activities of natural progesterone (P) and progestins. The aim of this article consists of synthesizing the principal aspects of pharmacology and metabolism of P and progestins related to the clinical consequences of their use.
EVIDENCE ACQUISITION
We review scientific literature on the topic "progestins," evaluating the most relevant data from original articles, reviews, and meta-analyses.
EVIDENCE SYNTHESIS
Progestins represent a specific class of synthetic analogues of P clinically employed (alone or associated with estrogens) to manage several gynecological conditions, for instance multiple abortions, luteal phase defect, premenstrual syndrome, abnormal uterine bleeding, endometriosis, and menopause (for hormone replacement therapy). Besides their use in the field of contraception, many non-contraceptive benefits of estroprogestins are mostly due to the activities of progestins. Pharmacological characteristics, dosage and individual metabolism could be listed among the principal aspects influencing their clinical effects.
CONCLUSIONS
The choice of each progestin according to its pharmacological profile is crucial for the appropriate management of any gynecological condition. An aware knowledge of these compounds is fundamental to hone medical practice.
Topics: Contraception; Estrogens; Female; Humans; Pregnancy; Progesterone; Progesterone Congeners; Progestins
PubMed: 34180615
DOI: 10.23736/S2724-606X.21.04881-8 -
Human Reproduction (Oxford, England) Jun 2023Does YAP1 inhibition alleviate progesterone resistance in endometriosis?
STUDY QUESTION
Does YAP1 inhibition alleviate progesterone resistance in endometriosis?
SUMMARY ANSWER
YAP1 inhibition reduces progesterone resistance in vitro and in vivo.
WHAT IS KNOWN ALREADY
Progesterone resistance not only causes treatment failure for endometriosis but also inhibits eutopic endometrial cell proliferation, dysregulates decidualization, and reduces the success rates of pregnancy. Hippo/yes-associated protein 1 (YAP1) signaling pathway plays an important role in the pathogenesis of endometriosis.
STUDY DESIGN, SIZE, DURATION
Paraffin-embedded tissues containing paired endometriotic and endometrial specimens (n = 42) and serum samples isolated from normal controls (n = 15) or endometriotic patients with (n = 25) or without (n = 21) prior dienogest treatment were analyzed. A mouse model of endometriosis was also used to evaluate the effects of YAP1 inhibition on progesterone resistance.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Primary endometriotic and endometrial stromal cells treated with YAP1 inhibitor or miR-21 mimic/inhibitor were used for the in vitro studies including decidualization induction, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation. Tissue specimens and serum from human and mouse were used for immunohistochemistry staining, exosome isolation, and microRNA (miRNA) quantification, respectively.
MAIN RESULTS AND THE ROLE OF CHANCE
Herein, we report, by using ChIP-PCR and RNA-IP, that YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. Upregulation of miR-21-5p not only reduces PGR expression but also inhibits endometrial stromal cell decidualization. Indeed, levels of YAP1 and miR-21-5p are inversely correlated with the level of PGR in human endometrial samples. In contrast, knockdown of YAP1 or treatment with verteporfin (VP), a YAP1 inhibitor, reduces miR-21-5p expression, thus leading to an increase in PGR expression in ectopic endometriotic stromal cells. In the mouse model of endometriosis, treatment with VP increases PGR expression and enhances decidualization. More importantly, VP synergistically increases the treatment effect of progestin in causing the regression of endometriotic lesions and improves the decidualization capability of the endometrium. Interestingly, treatment with dienogest, a synthetic progestin, reduces YAP1 and miR-21-5p expression in human cells and in the mouse model of endometriosis. Patients who received dienogest treatment for 6 months show a significant decrease in serum extracellular vesicle-associated miR-21-5p level.
LARGE SCALE DATA
A public dataset (GSE51981) containing a large cohort of endometriotic tissues is available from the Gene Expression Omnibus (GEO).
LIMITATIONS, REASONS FOR CAUTION
A large cohort of clinical samples is needed to verify the current diagnostic value of miR-21-5p in future studies.
WIDER IMPLICATIONS OF THE FINDINGS
The reciprocal regulation of YAP1 and PGR suggests that combined YAP1 inhibitor and progestin may be a better therapeutic approach for treating endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Ministry of Science and Technology, Taiwan (MOST-111-2636-B-006-012, MOST-111-2314-B-006-075-MY3, and MOST-106-2320-B-006-072-MY3). The authors have no conflict of interest to disclose.
Topics: Pregnancy; Female; Humans; Animals; Mice; Endometriosis; Progestins; Endometrium; MicroRNAs; Progesterone; Transcription Factors; Stromal Cells
PubMed: 37071897
DOI: 10.1093/humrep/dead071 -
Current Opinion in Obstetrics &... Jun 2024The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative... (Review)
Review
PURPOSE OF REVIEW
The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative approach to the personalization of ovarian stimulation.
RECENT FINDINGS
Based on the ability of progesterone to inhibit ovulation, progestins have been used in ovarian stimulation (OS) follicular protocols to prevent a luteinizing hormone surge in patients undergoing in vitro fertilization (IVF), as an alternative to gonadotropin-releasing hormone (GnRH) analogue administration. This review explores the different types of progestogen protocols and their efficacy depending on the type of population or reproductive procedure in which they are administered and in comparison with that of GnRH analogues. Their effect on oocytes and embryos and their safety and cost-effectiveness are also analyzed.
SUMMARY
Progestins have proven their effectiveness as a gonadotropin adjuvant in terms of ovarian response, reproductive outcome, and safety. In addition, they offer the convenience of oral administration and a lower cost than GnRH analogues. Whereas oocytes or embryos should be vitrified as it displaces the receptive period with the consequent asynchrony between embryo and endometrium. The evidence endorses progestins as a more friendly approach to OS, especially when frozen-thawed embryo transfer is planned.
Topics: Humans; Female; Ovulation Induction; Progestins; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Pregnancy
PubMed: 38295019
DOI: 10.1097/GCO.0000000000000941 -
Archives of Gynecology and Obstetrics Mar 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose... (Meta-Analysis)
Meta-Analysis
PURPOSE
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose of this study is to evaluate whether PPOS is as effective as conventional protocols (without GnRHa downregulation).
METHOD
Search terms included "medroxyprogesterone", "dydrogesterone", "progestin-primed ovarian stimulation", "PPOS", "oocyte retrieval", "in vitro fertilization", "IVF", "ICSI", "ART", and "reproductive". The selection criteria were nonrandomized studies and randomized controlled studies. For data collection and analysis, the Review Manager software, Newcastle-Ottowa Quality Assessment Scale and GRADE approach were used.
RESULTS
The clinical pregnancy rates were not significantly different in either RCTs or NRCTs [RR 0.96, 95% CI (0.69-1.33), I = 71%, P = 0.81]; [RR 0.99, 95% CI (0.83-1.17), I = 38%, P = 0.88]. The live birth rates of RCTs and NRCTs did not differ [RCT: RR 1.08, 95% CI (0.74, 1.57), I = 66%, P = 0.69; NRCT: OR 1.03 95% CI 0.84-1.26), I = 50%, P = 0.79]. The PPOS protocol had a lower rate of OHSS [RR 0.52, 95% CI (0.36-0.75), I = 0%, P = 0.0006]. The secondary results showed that compared to the control protocol, the endometrium was thicker [95% CI (0.00-0.78), I = 0%, P = 0.05], the number of obtained embryos was higher [95% CI (0.04-0.65), I = 17%, P = 0.03] and more hMG was needed [in NRCT: 95% CI (307.44, 572.73), I = 0%, P < 0.00001] with the PPOS protocol.
CONCLUSION
The PPOS protocol produces more obtained embryos and a thicker endometrium than the control protocol, with a lower rate of OHSS and an equal live birth rate. The PPOS protocol could be a safe option as a personalized protocol for infertile patients.
TRIAL REGISTRATION
Registration at PROSPERO: CRD42020176577.
Topics: Dydrogesterone; Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Reproduction
PubMed: 33433705
DOI: 10.1007/s00404-020-05939-y -
Current Opinion in Obstetrics &... Aug 2019Postmenopausal endometriosis is a gynecologic disease, affecting 2-5% of postmenopausal woman. Current literature assessing the prevalence, pathogenesis, and treatment... (Review)
Review
PURPOSE OF REVIEW
Postmenopausal endometriosis is a gynecologic disease, affecting 2-5% of postmenopausal woman. Current literature assessing the prevalence, pathogenesis, and treatment of this uncommon condition is limited, stressing the necessity for future research. This review examines the current literature on postmenopausal endometriosis to help inform clinical decision-making and point to novel approaches for treatment and management.
RECENT FINDINGS
Although one unifying theory to explain the pathogenesis of endometriotic lesions has not been elucidated, estrogen dependence is central to the pathophysiological process. The total quantity of estrogen production is mediated by multiple enzymes in complex pathways. Recent studies have confirmed the presence of these necessary enzymes in endometriotic lesions thereby suggesting a local source of estrogen and a likely pathogenic contributor. More research is needed to fully elucidate the mechanism of local estrogen biosynthesis; however, the current data provide possible explanations for the presence of postmenopausal endometriosis in an otherwise systemically hypoestrogenic environment.
SUMMARY
All suspected endometriosis lesions should be surgically excised for optimization of treatment and prevention of malignant transformation. If hormone replacement therapy is initiated, combined estrogen and progestin is recommended, even in the setting of previous hysterectomy, given the risk of disease reactivation and malignant transformation of endometriotic lesions. Further research is needed to understand the true prevalence, cause, and progression in this patient demographic. Histologic studies evaluating tissue lesions and peritoneal fluid for estrogen receptors, estrogen metabolizing enzymes, immune cells, and nerve fibers will aide in clinical management and treatment planning.
Topics: Biopsy; Cell Transformation, Neoplastic; Disease Progression; Endometriosis; Estrogens; Female; Hormone Replacement Therapy; Humans; Hysterectomy; Postmenopause; Prevalence; Progestins; Receptors, Estrogen; Treatment Outcome
PubMed: 31276453
DOI: 10.1097/GCO.0000000000000548