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International Journal of Molecular... Jul 2022Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial... (Review)
Review
Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
Topics: Female; Hormones; Humans; Infant, Newborn; Pregnancy; Progesterone; Progestins
PubMed: 35887338
DOI: 10.3390/ijms23147989 -
International Journal of Molecular... Apr 2023Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used... (Review)
Review
Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.
Topics: Humans; Female; Endometriosis; Progesterone; Progestins; Receptors, Progesterone; Endometrium
PubMed: 37108154
DOI: 10.3390/ijms24086992 -
Journal of Obstetrics and Gynaecology... Dec 2019The aim of this guideline is to aid primary care physicians and gynaecologists in the initial evaluation of women with suspected endometrial hyperplasia, to recommend...
OBJECTIVE
The aim of this guideline is to aid primary care physicians and gynaecologists in the initial evaluation of women with suspected endometrial hyperplasia, to recommend the use of the 2014 World Health Organization classification for endometrial hyperplasia by all health care providers, and to guide the optimal treatment of women diagnosed with endometrial hyperplasia.
INTENDED USERS
Physicians, including gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; medical trainees, including medical students, residents, and fellows; and all other health care providers.
TARGET POPULATION
Adult women (18 years and older) presenting with suspected or confirmed endometrial hyperplasia.
OPTIONS
The discussion relates to the medical therapy as well as surgical treatment options for women with and without atypical endometrial hyperplasia.
EVIDENCE
For this guideline, relevant studies were searched in PubMed, Cochrane Wiley, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials, human subjects, and published since 2000: (endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrial sampling, endometrial curettage, diagnosis) AND (treatment, progestin therapy, surgery, LNG-IUS, aromatase inhibitors, metformin ), AND (obesity). The search was performed in April 2018. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2152, and 82 studies were included in this review.
VALIDATION METHODS
The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The interpretation of strong and weak recommendations was also included. The Summary of Findings is available upon request.
BENEFITS, HARMS, AND/OR COSTS
It is expected that this guideline will benefit women with endometrial hyperplasia. This should guide patient informed consent before both medical and surgical management of this condition.
GUIDELINE UPDATE
Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.
SUMMARY STATEMENTS
RECOMMENDATIONS.
Topics: Endometrial Hyperplasia; Female; Humans; Hysterectomy; Levonorgestrel; Progestins
PubMed: 31785798
DOI: 10.1016/j.jogc.2019.03.025 -
Medicina (Kaunas, Lithuania) Sep 2022Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended... (Review)
Review
Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical-pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.
Topics: Conservative Treatment; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Metformin; Pregnancy; Progestins; Retrospective Studies; Treatment Outcome
PubMed: 36143933
DOI: 10.3390/medicina58091256 -
Women's Health (London, England) 2023The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to... (Review)
Review
The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-β-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-β-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.
Topics: Female; Humans; Progestins; Estetrol; Estrogens; Ethinyl Estradiol; Contraceptives, Oral, Combined; Estradiol
PubMed: 36744531
DOI: 10.1177/17455057221147388 -
International Journal of Molecular... Feb 2022Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has... (Review)
Review
Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has increased in young women, as well in recent decades, with an estimated rate of 4% in those under 40 years of age. Factors involved in this increase, particularly in resource-rich countries, include delayed childbearing and the rise in obesity. The new molecular classification of EC should help to personalize treatment, through appropriate candidate selection. With the currently available evidence, the use of oral progestin either alone or in combination with other drugs such as metformin, levonorgestrel-releasing intrauterine devices and hysteroscopic resection, seems to be feasible and safe in women with early-stage EC limited to the endometrium. However, there is a lack of high-quality evidence of the efficacy and safety of conservative management in EC. Randomized clinical trials in younger women and obese patients are currently underway.
Topics: Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Levonorgestrel; Progestins
PubMed: 35269674
DOI: 10.3390/ijms23052531 -
Sante Publique (Vandoeuvre-les-Nancy,... 2023This article focuses on the hierarchical structure of users of a synthetic progestin, Homodeor and its effects on the construction of a pharmacovigilance plan by a...
This article focuses on the hierarchical structure of users of a synthetic progestin, Homodeor and its effects on the construction of a pharmacovigilance plan by a French health agency, at a time when an institutional desire is being expressed to work more closely with all patient associations. This case study is mainly on a qualitative survey led by interviewing agents, health professionals and user representatives, which aimed to explore the relationships and representations developed around this issue. Despite the diversity of progestin use, a hierarchy between the different user groups was gradually established. The pharmacovigilance measures were designed for a specific group of patients, presented as the ideal users of the drug. The case of Homodeor makes it possible to highlight the dynamics of competition between groups of patients, and more broadly, the challenges of taking minority groups into account in health policies in the light of their development context.
Topics: Humans; Progestins; Health Personnel; Surveys and Questionnaires; Health Facilities; Pharmacovigilance
PubMed: 37336747
DOI: 10.3917/spub.hs2.0049 -
The Journal of Steroid Biochemistry and... Oct 2022Research leading to the discovery and characterization of progesterone (P4) began in the mid 1800 s and followed a path carved by key discoveries in the burgeoning... (Review)
Review
Research leading to the discovery and characterization of progesterone (P4) began in the mid 1800 s and followed a path carved by key discoveries in the burgeoning field of endocrinology. The primary observations leading to the discovery of P4 was that the maternal corpus luteum (CL) is necessary for the establishment and maintenance of pregnancy. Experiments in animal models exploring the consequence of CL ablation and the effects of treatment with CL extract soon followed and formed the basis for the eventual isolation and characterization in 1930 s of the CL hormone, initially referred to as progestin, and subsequently named progesterone. In the following decades research into the physiology, biochemistry and molecular biology of P4 in the context of pregnancy provided fundamental insights into the hormonal control of pregnancy establishment, maintenance and termination. This review highlights the work of pioneering researchers and their seminal discoveries in the research history of P4.
Topics: Animals; Corpus Luteum; Female; Pregnancy; Progesterone; Progestins
PubMed: 35902065
DOI: 10.1016/j.jsbmb.2022.106157 -
Menopause (New York, N.Y.) Apr 2023The menopausal hormone therapy (MHT) association with breast cancer has been controversial for more than 40 years. Most recently, findings from cohort studies have been... (Meta-Analysis)
Meta-Analysis
IMPORTANCE AND OBJECTIVE
The menopausal hormone therapy (MHT) association with breast cancer has been controversial for more than 40 years. Most recently, findings from cohort studies have been discordant compared with those from the Women's Health Initiative (WHI) randomized trials. In cohort studies, both estrogen therapy and estrogen plus progestin were associated with higher breast cancer incidence. In contrast, in the WHI randomized trials, findings for estrogen plus progestin are concordant with cohort study reports, whereas estrogen therapy significantly reduced breast cancer incidence. In addition, concerns have been raised regarding the WHI findings from both trials. In this report, we briefly summarize findings for MHT on breast cancer from cohort studies and the WHI randomized trials. The report focus is addressing, point-by-point, concerns raised regarding the WHI findings.
METHODS
For cohort studies, we relied on the latest findings from (1) the meta-analysis of the Collaborative Group on Hormonal Factors in Breast Cancer and (2) the Million Women's Study. To identify commentaries and editorials, "Menopause" and "Climacteric" were searched from 2002 to present; PubMed and Google Scholar were searched for commentaries, editorials, and breast cancer, MHT, estrogen, conjugated equine estrogen, estradiol, "hormone replacement therapy," and "HRT."
DISCUSSION AND CONCLUSIONS
Thirty commentaries challenging WHI findings were identified. All were reviewed, and issues needing response were identified. Findings from the meta-analysis from the Collaborative Group on Hormonal Factors in Breast Cancer and the Million Women Study were summarized and compared with finding in the two WHI randomized trials evaluating estrogen therapy and estrogen plus progestin. Based on the randomized clinical trials, estrogen therapy, for women with prior hysterectomy, decreases breast cancer incidence and mortality. In contrast, estrogen plus progestin increases breast cancer incidence, which persists through two decades. Women considering estrogen plus progestin use for vasomotor symptoms should understand the breast cancer risk.
Topics: Humans; Female; Progestins; Cohort Studies; Estrogen Replacement Therapy; Randomized Controlled Trials as Topic; Women's Health; Menopause; Estrogens; Neoplasms; Breast Neoplasms
PubMed: 36727752
DOI: 10.1097/GME.0000000000002154 -
Best Practice & Research. Clinical... Nov 2020It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory... (Review)
Review
It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.
Topics: Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Humans; Progesterone; Progestins
PubMed: 32732107
DOI: 10.1016/j.bpobgyn.2020.05.003