Progesterone

The endometrium is crucial for the perpetuation of human species. It is a complex and dynamic tissue lining the inner wall of the uterus, regulated throughout a woman's life based on estrogen and progesterone fluctuations. During each menstrual cycle, this multicellular tissue undergoes cyclical changes, including regeneration, differentiation in order to allow egg implantation and embryo development, or shedding of the functional layer in the absence of pregnancy. The biology of the endometrium relies on paracrine interactions between epithelial and stromal cells involving complex signaling pathways that are modulated by the variations of estrogen and progesterone levels across the menstrual cycle. Understanding the complexity of estrogen and progesterone receptor signaling will help elucidate the mechanisms underlying normal reproductive physiology and provide fundamental knowledge contributing to a better understanding of the consequences of hormonal imbalances on gynecological conditions and tumorigenesis. In this narrative review, we delve into the physiology of the endometrium, encompassing the complex signaling pathways of estrogen and progesterone.

ObjectivesTo evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.DesignThe PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.Setting34 UK hospitals.Participants405 women of reproductive age undergoing conservative surgery for endometriosis.InterventionsParticipants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.Main outcome measuresThe primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).Results405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).ConclusionsPostoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.Trial registrationISRCTN registry ISRCTN97865475.

Endometriosis is a refractory estrogen-dependent gynecological disease in which ovarian endometriosis(OE) is the most common, and the main cell components are endometrial epithelial cells and stromal cells. However, constructing ectopic endometrial epithelial cell models in basic studies is still challenging. In this study, we explored the feasibility and influencing factors of constructing and validating eutopic and ectopic endometrial organoid models of OE as in-vitro models. Eutopic and ectopic endometrial tissues of OE patients were selected to establish organoids. Morphologically, the organoids showed a three-dimensional glandular structure with vacuoles or cystic irregularities, and the histological features of the epithelial organoids in endometriosis were well preserved. Immunofluorescence showed positive expression of epithelial markers and estrogen/progesterone receptors. Genetic identification revealed a 100% match between endometriosis epithelial organoids and endometrial tissue, indicating a common origin. The effects of estrogen and progesterone on the proliferation and secretion of organoids differed with the change in concentration. The successful construction of ectopic endometrial organoids provides a new in vitro model for drug intervention and mechanism study of ovarian endometriosis.

BackgroundA greater understanding of gestational age-adjusted steroid profiles in preterm neonates is needed to inform diagnosis, optimal timing, dosage, and duration of postnatal steroid therapy for preterm infants with adrenal insufficiency. Therefore, we evaluated changes in steroid profiles using newborn screening dried blood spots (DBS) to determine the impact of prematurity on fetal adrenal function.MethodsCortisol and its biosynthetic precursors were quantified in 813 anonymized DBS from newborns between 23 to 42 weeks of gestation, collected within 72 hours of birth and again approximately two weeks later. Steroid quantification was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with analyses stratified by gestational and postnatal ages.ResultsExtremely preterm infants often had elevated cortisol levels, with a general decline as gestational age increased. Levels of 17-hydroxyprogesterone (17OHP4) and corticosterone were significantly higher in most preterm newborns, with 17OHP4 showing the strongest inverse correlation with gestational age. In contrast, aldosterone levels remained unaffected by gestational age.ConclusionsElevations in 17OHP4 and corticosterone, rather than cortisol alone, reflect prematurity's effect on adrenal sufficiency. Preterm infants with high cortisol and elevated corticosterone and 17OHP4 levels may struggle to meet their physiological cortisol needs through the hypothalamic-pituitary-adrenal axis, increasing the risk of adrenal crises. These findings provide important insights to guide the management of adrenal insufficiency in preterm neonates.ImpactThe increasing survival of preterm infants born at earlier gestational ages presents clinicians with the complex challenge of distinguishing normal from abnormal adrenal function, a determination which may be critical for survival. Our study advances the understanding of adrenal dysfunction in this population by employing analytical methods rooted in the steroid biosynthesis pathway's maturation. By utilizing techniques traditionally used to diagnose congenital adrenal hyperplasia (CAH), we provide actionable guidance for interpreting steroid data in preterm infants, offering a practical framework for improved clinical decision-making.