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Climacteric : the Journal of the... Aug 2018Progesterone is a neurosteroid and a neuroactive steroid, produced primarily by the corpus luteum and the placenta. In some animal models, progesterone affects cognitive... (Review)
Review
Progesterone is a neurosteroid and a neuroactive steroid, produced primarily by the corpus luteum and the placenta. In some animal models, progesterone affects cognitive performance, and its potential role in human cognition is especially germane to women. This role can be investigated through associations between peripheral concentrations of progesterone in blood or saliva and neuropsychological test results, through differences in cognitive profiles between women using menopausal hormone therapy with and without a progestogen, and through clinical trials. In naturally cycling reproductive-age women and pregnant women, there is no consistent relation between progesterone levels and cognition. In postmenopausal women within 6 years of menopause and not using hormone therapy, progesterone levels are positively associated with verbal memory and global cognition, but reported associations in older postmenopausal women are null. Some observational studies of postmenopausal women using hormone therapy raise concern of a small deleterious cognitive effect of progestogen (medroxyprogesterone acetate was most often reported in these studies), but this association may due to confounding factors. Small, short-term clinical trials of progesterone show no meaningful effect on cognition. The quality of evidence is low, but overall findings do not reveal consistent, clinically important effects of progesterone on cognitive function in women.
Topics: Animals; Cognition; Cognition Disorders; Estrogen Replacement Therapy; Female; Humans; Medroxyprogesterone Acetate; Memory; Neuropsychological Tests; Postmenopause; Pregnancy; Progesterone; Progestins; Randomized Controlled Trials as Topic
PubMed: 29852783
DOI: 10.1080/13697137.2018.1476484 -
BMJ (Clinical Research Ed.) Jan 2019To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. (Comparative Study)
Comparative Study Observational Study
OBJECTIVE
To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.
DESIGN
Two nested case-control studies.
SETTING
UK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.
PARTICIPANTS
80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls.
MAIN OUTCOME MEASURES
Venous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.
RESULTS
Overall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiol had a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).
CONCLUSIONS
In the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.
Topics: Administration, Cutaneous; Adult; Aged; Case-Control Studies; Estrogens; Female; Hormone Replacement Therapy; Humans; Medroxyprogesterone Acetate; Menopause; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; United Kingdom; Venous Thromboembolism
PubMed: 30626577
DOI: 10.1136/bmj.k4810 -
Women's Health (London, England) Jan 2016Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of... (Review)
Review
Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations.
Topics: Antifibrinolytic Agents; Contraceptives, Oral, Hormonal; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Women's Health
PubMed: 26695687
DOI: 10.2217/whe.15.100 -
BMJ (Clinical Research Ed.) Mar 2024To assess the risk of intracranial meningioma associated with the use of selected progestogens.
OBJECTIVE
To assess the risk of intracranial meningioma associated with the use of selected progestogens.
DESIGN
National case-control study.
SETTING
French National Health Data System (ie, ).
PARTICIPANTS
Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls).
MAIN OUTCOME MEASURES
Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association.
RESULTS
Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use.
CONCLUSIONS
Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.
Topics: Female; Humans; Middle Aged; Progestins; Progesterone; Levonorgestrel; Meningioma; Medroxyprogesterone Acetate; Dydrogesterone; Medrogestone; Promegestone; Case-Control Studies; Meningeal Neoplasms
PubMed: 38537944
DOI: 10.1136/bmj-2023-078078 -
Global Health, Science and Practice Mar 2018DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many...
DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many women like, including cost and time savings, and has the potential to be delivered by a range of health care cadres in a variety of service delivery channels.
Topics: Contraception; Contraceptive Agents; Contraceptive Agents, Female; Humans; Injections; Medroxyprogesterone Acetate
PubMed: 29602863
DOI: 10.9745/GHSP-D-18-00050 -
Endocrine Reviews Feb 2018Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition,... (Review)
Review
Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are rather limited in settings with restricted economic resources that frequently overlap with areas of high HIV-1 prevalence. The predominant contraceptive used in sub-Saharan Africa is the progestin-only three-monthly injectable depot medroxyprogesterone acetate. Determination of whether HCs affect HIV-1 acquisition has been hampered by behavioral differences potentially confounding clinical observational data. Meta-analysis of these studies shows a significant association between depot medroxyprogesterone acetate use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate, although data for norethisterone enanthate are limited. Susceptibility to HIV-1 and other sexually transmitted infections may, however, be dependent on the type of progestin present in the formulation. Several underlying biological mechanisms that may mediate the effect of HCs on HIV-1 and other sexually transmitted infection acquisition have been identified in clinical, animal, and ex vivo studies. A substantial gap exists in the translation of basic research into clinical practice and public health policy. To bridge this gap, we review the current knowledge of underlying mechanisms and biological effects of commonly used progestins. The review sheds light on issues critical for an informed choice of progestins for the identification of safe, effective, acceptable, and affordable contraceptive methods.
Topics: Animals; Contraception; Contraceptive Agents, Female; Disease Susceptibility; Dose-Response Relationship, Drug; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Medroxyprogesterone Acetate; Progestins
PubMed: 29309550
DOI: 10.1210/er.2017-00103 -
World Journal of Clinical Cases Aug 2023Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide, and early-stage high-risk endometrial cancer has a poor prognosis. Adjuvant...
BACKGROUND
Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide, and early-stage high-risk endometrial cancer has a poor prognosis. Adjuvant treatments after surgery, such as chemotherapy and radiotherapy, have been widely used in clinical practice to improve patient survival. Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer. However, its efficacy, safety, and long-term prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial. Therefore, this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with early-stage high-risk endometrial cancer and evaluate its safety.
AIM
To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.
METHODS
We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022. The control group (100 patients) underwent conventional surgical treatment, and the study group (100 patients) was administered adjuvant medroxyprogesterone acetate tablets on top of the control group. The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients. The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.
RESULTS
According to the Cox regression analysis, age [hazard ratio (HR) = 4.636, 95% confidence interval (95%CI): 1.411-15.237], pathological type (HR = 6.943, 95%CI: 2.299-20.977), molecular typing (HR = 5.789, 95%CI: 3.305-10.141), and myometrial infiltration (HR = 5.768, 95%CI: 1.898-17.520) were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.
CONCLUSION
Age, pathological type, molecular typing, and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer. The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.
PubMed: 37637703
DOI: 10.12998/wjcc.v11.i23.5447 -
Steroids Nov 2022Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to understand progestin pharmacokinetics and to correct for... (Review)
Review
Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to understand progestin pharmacokinetics and to correct for unreliable self-reporting of contraceptive use by study participants. Many such studies are focussed on the three-monthly progestin-only intramuscular (IM) injectable contraceptive depot medroxyprogesterone acetate (DMPA-IM). Methods commonly used to measure serum MPA levels include liquid chromatography coupled to mass spectrometry (LC/MS) and radioimmunoassay (RIA); however, RIA methods have not been used in recent years. We review the available literature and find that these methods vary widely in terms of use of organic solvent extraction, use of derivitization and choice of organic solvent and chromatography columns. There is a lack of standardization of LC/MS methodology, including a lack of detailed extraction protocols. Limited evidence suggests that RIA, without organic solvent extraction, likely over-estimates progestin levels. Maximum MPA concentrations in the first two weeks post-injection show wide inter-individual and inter-study variation, regardless of quantification method used. Standardization of quantification methods and sampling time post-injection is required to improve interpretation of clinical data, in particular the side effects arising at different times depending on the pharmacokinetic profile unique to injectable contraceptives.
Topics: Contraceptive Agents; Contraceptive Agents, Female; Female; Humans; Medroxyprogesterone Acetate; Progestins; Radioimmunoassay; Solvents
PubMed: 35964796
DOI: 10.1016/j.steroids.2022.109100 -
Best Practice & Research. Clinical... Aug 2014Progestin-only contraceptive injectables and implants are highly effective, longer-acting contraceptive methods that can be used by most women in most circumstances.... (Review)
Review
Progestin-only contraceptive injectables and implants are highly effective, longer-acting contraceptive methods that can be used by most women in most circumstances. Globally, 6% of women using modern contraception use injectables and 1% use implants. Injectables are the predominant contraceptive method used in sub-Saharan Africa, and account for 43% of modern contraceptive methods used. A lower-dose, subcutaneous formulation of the most widely used injectable, depot-medroxyprogesterone acetate, has been developed. Implants have the highest effectiveness of any contraceptive method. Commodity cost, which historically limited implant availability in low-resource countries, was markedly lowered between 2012 and 2013. Changes in menstrual bleeding patterns are extremely common with both methods, and a main cause of discontinuation. Advice from normative bodies differs on progestin-only contraceptive use by breastfeeding women 0-6 weeks postpartum. Whether these methods are associated with HIV acquisition is a controversial issue, with important implications for sub-Saharan Africa, which has a disproportionate burden of both human immunodeficiency virus (HIV) and maternal mortality.
Topics: Breast Feeding; Contraception; Contraceptive Agents, Female; Delayed-Action Preparations; Drug Implants; Female; Humans; Injections, Intramuscular; Injections, Subcutaneous; Medroxyprogesterone Acetate; Pregnancy; Progesterone Congeners
PubMed: 24996766
DOI: 10.1016/j.bpobgyn.2014.05.003 -
Obstetrics and Gynecology May 2022Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.
OBJECTIVE
Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.
METHODS
We conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.
RESULTS
Of participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).
CONCLUSION
Recent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.
Topics: Cohort Studies; Contraceptive Agents, Female; Delayed-Action Preparations; Female; Humans; Incidence; Leiomyoma; Medroxyprogesterone; Medroxyprogesterone Acetate
PubMed: 35576339
DOI: 10.1097/AOG.0000000000004745