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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 -
The Journal of Clinical Endocrinology... Oct 2023Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital...
CONTEXT
Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin.
OBJECTIVE
To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH.
METHODS
This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone.
RESULTS
8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57%; 17OHP, -69%; and androstenedione, -58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone.
CONCLUSION
Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.
Topics: Male; Adult; Humans; Female; Adolescent; Androgens; Adrenal Hyperplasia, Congenital; Androstenedione; 17-alpha-Hydroxyprogesterone; Testosterone; Adrenocorticotropic Hormone
PubMed: 37216921
DOI: 10.1210/clinem/dgad270 -
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 -
Nature Communications Aug 2023Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine...
Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine biology. Using rapid immunoprecipitation and mass spectrometry (RIME) and co-immunoprecipitation, we identified TRIM28 (Tripartite motif containing 28) as a protein which complexes with ERα and PR in the regulation of uterine function. Impairment of TRIM28 expression results in the inability of the uterus to support early pregnancy through altered PR and ERα action in the uterine epithelium and stroma by suppressing PR and ERα chromatin binding. Furthermore, TRIM28 ablation in PR-expressing uterine cells results in the enrichment of a subset of TRIM28 positive and PR negative pericytes and epithelial cells with progenitor potential. In summary, our study reveals the important roles of TRIM28 in regulating endometrial cell composition and function in women, and also implies its critical functions in other hormone regulated systems.
Topics: Pregnancy; Female; Humans; Estrogen Receptor alpha; Estradiol; Uterus; Progesterone; Receptors, Progesterone; Epithelium; Tripartite Motif-Containing Protein 28
PubMed: 37528140
DOI: 10.1038/s41467-023-40395-7 -
Frontiers in Allergy 2024Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late... (Review)
Review
Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for or tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.
PubMed: 38720769
DOI: 10.3389/falgy.2024.1384140 -
Nutrients Aug 2023Creatine supplementation improves anaerobic performance and recovery; however, to date, these outcomes have not been well explored in females. This study evaluated the... (Randomized Controlled Trial)
Randomized Controlled Trial
Creatine supplementation improves anaerobic performance and recovery; however, to date, these outcomes have not been well explored in females. This study evaluated the effect of creatine monohydrate loading on exercise recovery, measured by heart rate variability (HRV) and repeated sprint performance, in women across the menstrual cycle. In this randomized, double-blind, cross-over study, 39 women (mean ± standard deviation: age: 24.6 ± 5.9 years, height: 172.5 ± 42.3 cm, weight: 65.1 ± 8.1 kg, BF: 27.4 ± 5.8%) were randomized to a creatine monohydrate ( = 19; 20 g per day in 4 × 5 g doses) or non-caloric PL group ( = 20). HRV was measured at rest and after participants completed a repeated sprint cycling test (10 × 6 s maximal sprints). Measurements were conducted before and after supplementation in the follicular/low hormone and luteal/high hormone phases. Creatine monohydrate supplementation did not influence HRV values, as no significant differences were seen in HRV values at rest or postexercise. For repeated sprint outcomes, there was a significant phase × supplement interaction ( = 0.048) for fatigue index, with the greatest improvement seen in high hormone in the creatine monohydrate group (-5.8 ± 19.0%) compared to changes in the PL group (0.1 ± 8.1%). Sprint performance and recovery were reduced by the high hormone for both groups. Though not statistically significant, the data suggests that creatine monohydrate could help counteract performance decrements caused by the high hormone. This data can help inform creatine monohydrate loading strategies for females, demonstrating potential benefits in the high hormone phase.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Creatine; Cross-Over Studies; Menstrual Cycle; Bicycling; Dietary Supplements; Progesterone
PubMed: 37630756
DOI: 10.3390/nu15163567 -
International Journal of Molecular... Oct 2023Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes... (Review)
Review
Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes processes such as inflammation, progesterone resistance, angiogenesis, and cell proliferation. Epigenetic factors, particularly the dysregulation of microRNAs (miRNAs), have emerged as key factors in these mechanisms in endometriosis. This review aims to unveil the intricate molecular processes that control inflammation, progesterone resistance, and miRNA functions in endometriosis. In addition, it provides a comprehensive overview of the current understanding regarding the involvement of miRNAs in the inflammatory aspects of this condition. This synthesis encompasses research investigating the molecular underpinnings of inflammation, along with the biogenesis and roles of miRNAs in endometriosis. Furthermore, it examines human studies and functional analyses to establish the intricate connection between miRNAs, inflammation, and progesterone resistance in the context of endometriosis. The results highlight the significant impact of dysregulated miRNAs on the inflammatory pathways and hormonal imbalances characteristic of endometriosis. Consequently, miRNAs hold promise as potential non-invasive biomarkers and targeted therapeutic agents aimed at addressing inflammation and enhancing the response to progesterone treatment in individuals with endometriosis.
Topics: Female; Humans; MicroRNAs; Endometriosis; Uterine Diseases; Endometrium; Progesterone; Receptors, Progesterone
PubMed: 37834449
DOI: 10.3390/ijms241915001 -
BioRxiv : the Preprint Server For... Aug 2023Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain...
Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone. We measured the pain threshold daily for four days in ovariectomized, estrogen-primed animals treated with progesterone. The pain threshold was lower 2 days later and stayed that way for the duration of the testing. A specific progesterone-receptor (PR) agonist, segesterone, promoted pain, and mice lacking PR in the brain (PRKO) did not experience lowered pain threshold when treated with progesterone or segesterone. PR activation increased the cold sensitivity but did not affect the heat sensitivity and had a small effect on light sensitivity. Finally, we evaluated whether PR activation altered experimental migraine. Segesterone and nitroglycerin (NTG) when administered sequentially, reduced pain threshold but not separately. These studies have uncovered a pain-regulating function of PRs. Targeting PRs may provide a novel therapeutic avenue to treat chronic pain in women.
PubMed: 37609239
DOI: 10.1101/2023.08.04.552037