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European Journal of Sport Science Jul 2022Sex steroids, commonly referred to as sex hormones, are integral to the development and maintenance of the human reproductive system. In addition, male (androgens) and... (Review)
Review
Sex steroids, commonly referred to as sex hormones, are integral to the development and maintenance of the human reproductive system. In addition, male (androgens) and female (estrogens and progestogens) sex hormones promote the development of secondary sex characteristics by targeting a range of other tissues, including skeletal muscle. The role of androgens on skeletal muscle mass, function and metabolism has been well described in males, yet female specific studies are scarce in the literature. This narrative review summarises the available evidence around the mechanistic role of androgens, estrogens and progestogens in female skeletal muscle. An analysis of the literature indicates that sex steroids play important roles in the regulation of female skeletal muscle mass and function. The free fractions of testosterone and progesterone in serum were consistently associated with the regulation of muscle mass, while estrogens may be primarily involved in mediating the muscle contractile function in conjunction with other sex hormones. Muscle strength was however not directly associated with any hormone in isolation when at physiological concentrations. Importantly, recent evidence suggests that intramuscular sex hormone concentrations may be more strongly associated with muscle size and function than circulating forms, providing interesting opportunities for future research. By combining cross-sectional, interventional and mechanical studies, this review aims to provide a broad, multidisciplinary picture of the current knowledge of the effects of sex steroids on skeletal muscle in females, with a focus on the regulation of muscle size and function and an insight into their clinical implications. HighlightsFree testosterone, but not total testosterone, is associated with lean mass but not strength in pre- and post-menopausal females.Progesterone and estrogens may regulate muscle mass and strength, respectively, in females.Intra-muscular steroids may be more closely associated to muscle mass and strength, compared to systemic fractions.
Topics: Androgens; Cross-Sectional Studies; Estrogens; Female; Gonadal Steroid Hormones; Humans; Male; Muscle, Skeletal; Progesterone; Progestins; Steroids; Testosterone
PubMed: 33890831
DOI: 10.1080/17461391.2021.1921854 -
Contraception Dec 2016Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated... (Review)
Review
BACKGROUND
Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age.
OBJECTIVE
To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives.
METHODS
We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch and ring) and progestin-only methods (progestin-only pills, injectables, implants and progestin intrauterine devices).
RESULTS
Seven articles met inclusion criteria. All were case-control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately two to four times the risk of stroke compared with nonuse. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction.
CONCLUSION
Limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use COCs compared with nonuse. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes.
Topics: Contraceptive Devices, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Migraine Disorders; Myocardial Infarction; Progestins; Risk Assessment; Stroke
PubMed: 27153744
DOI: 10.1016/j.contraception.2016.04.016 -
International Journal of Gynecological... Nov 2020This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the... (Review)
Review
OBJECTIVES
This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify 'low-risk' cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers.
METHODS
PubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted.
RESULTS
Of 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as 'low-risk' by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with 'low-risk' features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated.
DISCUSSION
Molecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.
Topics: Biomarkers, Tumor; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Progestins; Risk Factors
PubMed: 32381512
DOI: 10.1136/ijgc-2020-001309 -
The Medical Journal of Malaysia Jul 2022Miscarriage affects up to 20% of pregnant women, resulting in substantial psychological repercussions in addition to inherent problems from bleeding and infection.... (Review)
Review
Miscarriage affects up to 20% of pregnant women, resulting in substantial psychological repercussions in addition to inherent problems from bleeding and infection. Preterm births constitute about 7-12% of all births but are over represented in terms of perinatal morbidity and mortality. Despite existing trials examining the use of progestogens in both these conditions, there is a dearth of guidelines for the practicing clinician. A systematic review of the literature was performed by an expert panel formed by the Obstetrical & Gynaecological Society of Malaysia from the inception of the databases searched up to February 2020, without language restrictions. The level of evidence and recommendations was determined by the panel and peer-reviewed by local and international experts. The use of progestogens is recommended in women with threatened miscarriages who have experienced previous miscarriage as luteal phase support in women undergoing assisted reproduction and in women with short cervix of <25mm in the midtrimester. In addition, it can be considered in women with recurrent miscarriage, where no other cause is identified. This article reviews the existing evidence including the guideline above and is intended to aid primary care doctors and obstetricians in their prescribing practices when managing these common conditions.
Topics: Abortion, Habitual; Female; Humans; Infant, Newborn; Malaysia; Pregnancy; Premature Birth; Progestins
PubMed: 35902945
DOI: No ID Found -
Frontiers in Endocrinology 2023
Topics: Contraceptive Agents; Progestins; Brain; Head
PubMed: 36798667
DOI: 10.3389/fendo.2023.1129203 -
Frontiers in Endocrinology 2021There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been... (Review)
Review
There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been reported with the older progestin only methods such as oral pills, injectables, and intrauterine devices, however, little is known about the risk with subdermal implants. In this review, we aim to update clinicians and researchers on the current evidence to support patient counseling and to inform future research directions. The available evidence of the association between the use of progestin subdermal implants and BC risk is discussed. We provide an overview of the potential role of endogenous progesterone in BC development. The chemical structure and molecular targets of synthetic progestins of relevance are summarized together with the preclinical and clinical evidence on their association with BC risk. We review all studies that investigated the action of the specific progestins included in subdermal implants. As well, we discuss the potential effect of the use of subdermal implants in women at increased BC risk, including carriers of BC susceptibility genetic mutations.
Topics: Breast Neoplasms; Clinical Trials as Topic; Contraceptive Agents, Female; Drug Implants; Female; Humans; Patient Education as Topic; Progesterone Congeners; Progestins; Risk Factors
PubMed: 34975755
DOI: 10.3389/fendo.2021.781066 -
American Family Physician Jul 2019
Review
Topics: Abortion, Spontaneous; Female; Humans; Live Birth; Obstetric Labor, Premature; Pregnancy; Progestins
PubMed: 31259502
DOI: No ID Found -
Pharmacology & Therapeutics Jun 2021Many different forms of hormonal contraception are used by millions of women worldwide. These contraceptives differ in the dose and type of synthetic progestogenic... (Review)
Review
Many different forms of hormonal contraception are used by millions of women worldwide. These contraceptives differ in the dose and type of synthetic progestogenic compound (progestin) used, as well as the route of administration and whether or not they contain estrogenic compounds. There is an increasing awareness that different forms of contraception and different progestins have different side-effect profiles, in particular their cardiovascular effects, effects on reproductive cancers and susceptibility to infectious diseases. There is a need to develop new methods to suit different needs and with minimal risks, especially in under-resourced areas. This requires a better understanding of the pharmacokinetics, metabolism, serum and tissue concentrations of progestins used in contraception as well as the biological activities of progestins and their metabolites via steroid receptors. Here we review the current knowledge on these topics and identify the research gaps. We show that there is a paucity of research on most of these topics for most progestins. We find that major impediments to clear conclusions on these topics include a lack of standardized methodologies, comparisons between non-parallel clinical studies and variability of data on serum concentrations between and within studies. The latter is most likely due, at least in part, to differences in intrinsic characteristics of participants. The review highlights the importance of insight on these topics in order to provide the best contraceptive options to women with minimal risks.
Topics: Contraception; Contraceptive Agents; Female; Humans; Progestins
PubMed: 33316287
DOI: 10.1016/j.pharmthera.2020.107789 -
Contraception Dec 2015Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely... (Review)
Review
BACKGROUND
Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely to result in ectopic pregnancies than some other methods such as combined hormonal and barrier contraceptives.
OBJECTIVE
To describe ectopic pregnancy risk associated with use of implants and progestin-only injectable contraceptives through a systematic review of published studies.
DATA SOURCES
We searched electronic databases for articles in any language published through May 2015 describing studies of progestin-only injectables and implants. We also searched bibliographies and review articles for additional studies.
STUDY SELECTION AND EXTRACTION
Studies that reported any pregnancies were included in the review. Independent data extraction was performed by two authors based on predefined data fields, and where possible, we calculated the proportion of pregnancies that were ectopic and the ectopic pregnancy incidence rate per 1000 woman-years.
RESULTS
Fifty-three studies of implants and 28 studies of injectables were identified; 79% reported pregnancy location. The proportion of ectopic pregnancy ranged from 0 to 100% with an incidence of 0-2.9 per 1000 woman-years in studies of marketed levonorgestrel implants. Studies of etonogestrel implants and the injectables, depot-medroxyprogesterone acetate and norethisterone enanthate, reported few ectopic pregnancies.
CONCLUSION
Progestin-only contraceptive implants and injectables protect against ectopic pregnancy by being highly effective in preventing pregnancy overall; however, the absolute risk of ectopic pregnancy varies by type of progestin. Risk of ectopic pregnancy should not be a deterrent for use or provision of these methods.
Topics: Contraception; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Incidence; Injections; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Pregnancy; Pregnancy, Ectopic; Progestins
PubMed: 26363431
DOI: 10.1016/j.contraception.2015.08.016 -
International Journal of Molecular... Jun 2023Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled...
Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E), MPA, or E + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E + MPA + cAMP) on levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on levels; (3) MPA-induced expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, overexpression in HESCs significantly enhanced prolactin (), insulin-like growth factor binding protein 1 (), and tissue factor () levels. Thrombin-induced interleukin 8 ( and prostaglandin-endoperoxide synthase 2 ( mRNA levels in control-vector-transfected HESCs were further increased by overexpression. In conclusion, these results supported that ZBTB16 is enhanced during decidualization, and long-term induction of ZBTB16 expression by pLARCs contributes to thrombin generation through enhancing tissue factor expression and inflammation by enhancing and levels in decidualized HESCs.
Topics: Female; Humans; Animals; Guinea Pigs; Progestins; Interleukin-8; Thrombin; Contraceptive Agents; Thromboplastin; Glucocorticoids; Cyclooxygenase 2; Endometrium; Estradiol; Inflammation; Stromal Cells; Cells, Cultured; Decidua; Medroxyprogesterone Acetate
PubMed: 37445713
DOI: 10.3390/ijms241310532