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Current Opinion in Obstetrics &... Jun 2024The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative... (Review)
Review
PURPOSE OF REVIEW
The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative approach to the personalization of ovarian stimulation.
RECENT FINDINGS
Based on the ability of progesterone to inhibit ovulation, progestins have been used in ovarian stimulation (OS) follicular protocols to prevent a luteinizing hormone surge in patients undergoing in vitro fertilization (IVF), as an alternative to gonadotropin-releasing hormone (GnRH) analogue administration. This review explores the different types of progestogen protocols and their efficacy depending on the type of population or reproductive procedure in which they are administered and in comparison with that of GnRH analogues. Their effect on oocytes and embryos and their safety and cost-effectiveness are also analyzed.
SUMMARY
Progestins have proven their effectiveness as a gonadotropin adjuvant in terms of ovarian response, reproductive outcome, and safety. In addition, they offer the convenience of oral administration and a lower cost than GnRH analogues. Whereas oocytes or embryos should be vitrified as it displaces the receptive period with the consequent asynchrony between embryo and endometrium. The evidence endorses progestins as a more friendly approach to OS, especially when frozen-thawed embryo transfer is planned.
Topics: Humans; Female; Ovulation Induction; Progestins; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Pregnancy
PubMed: 38295019
DOI: 10.1097/GCO.0000000000000941 -
Atherosclerosis Nov 2023Endothelial cells are important constituents of blood vessels and play a critical role in vascular homeostasis. They do not only control the exchanges between the blood... (Review)
Review
Endothelial cells are important constituents of blood vessels and play a critical role in vascular homeostasis. They do not only control the exchanges between the blood and the surrounding tissues, but are also essential in regulating blood flow, modulating immune-cell trafficking and controlling vascular growth and repair. Endothelial dysfunction leads to cardiovascular diseases and is characterized by deficiency in secretion of vasodilator molecules, elevated reactive oxygen species (ROS), expression of adhesion molecules and excretion of proinflammatory cytokines. The sex hormones, estrogens, androgens and progestogens, regulate endothelial functions. Because cardiovascular disease risk increases after menopause, it is believed that female hormones, estrogens and progestogens promote endothelial cell health and function whereas androgens, the male hormones, might be detrimental. However, as illustrated in the present review, the picture might not be that simple. In addition, sex influences endothelial cell physiology independently of sex hormones but at genetic level.
Topics: Male; Female; Humans; Progestins; Endothelial Cells; Sex Characteristics; Gonadal Steroid Hormones; Estrogens; Androgens
PubMed: 37770334
DOI: 10.1016/j.atherosclerosis.2023.117278 -
Physiological Reviews Jul 2024Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this... (Review)
Review
Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this end, hormones that affect the function of the gravid uterus, especially progesterone (P4), 17β-estradiol (E), oxytocin (OT), and prostaglandins (PGs), play pivotal roles. P4 via the nuclear P4 receptor (PR) promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Loss of the P4 block to parturition in association with a gain in prolabor actions of E are key transitions in the hormonal cascade leading to parturition. P4 withdrawal can occur through various mechanisms depending on species and physiological context. Parturition in most species involves inflammation within the uterine tissues and especially at the maternal-fetal interface. Local PGs and other inflammatory mediators may initiate parturition by inducing P4 withdrawal. Withdrawal of the P4 block is coordinated with increased E actions to enhance uterotonic signals mediated by OT and PGs to promote uterine contractions, cervix softening, and membrane rupture, i.e., labor. This review examines recent advances in research to understand the hormonal control of parturition, with focus on the roles of P4, E, PGs, OT, inflammatory cytokines, and placental peptide hormones together with evolutionary biology of and implications for clinical management of human parturition.
Topics: Parturition; Humans; Female; Pregnancy; Animals; Progesterone; Oxytocin; Uterus; Prostaglandins; Estradiol
PubMed: 38329421
DOI: 10.1152/physrev.00019.2023 -
PLoS Medicine Dec 2023Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the... (Observational Study)
Observational Study
BACKGROUND
Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently.
METHODS AND FINDINGS
Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur.
CONCLUSIONS
Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.
Topics: Female; Humans; Case-Control Studies; Central Nervous System Neoplasms; Denmark; Estrogen Replacement Therapy; Estrogens; Glioma; Meningeal Neoplasms; Meningioma; Menopause; Progestins; Risk Factors; Middle Aged
PubMed: 38113227
DOI: 10.1371/journal.pmed.1004321 -
Sexual Medicine Reviews Jun 2024Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits... (Review)
Review
INTRODUCTION
Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits inclusion in counseling on contraceptive options.
OBJECTIVES
The study sought to explore the impact of combined estrogens-progestin oral contraceptives on components of female sexuality, including sexual desire, anatomic genitourinary changes, lubrication, orgasm, provoked vestibulodynia, well-being, body image, partner preference, and relationship stability.
METHODS
A literature review was performed between April 2023 and January 2024 exploring the association between combined oral contraceptive pills and sexual health.
RESULTS
Although COCs decrease free testosterone, it is unclear if COCs affect sexual function, including desire. Antiandrogenic COCs do seem to have a negative effect on sexual arousal, lubrication, and orgasm. Provoked vestibulodynia may be related to early onset of COC use, low-estrogen pills, and antiandrogenic progestins. Emotional and sexual side effects are strong predictors of COC discontinuation. Longitudinal data indicate that using COCs when meeting and selecting a partner has implications on sexual satisfaction and relationship length. Analysis of data is complicated by various doses and forms of estrogen and progestin in COCs, which have changed over time.
CONCLUSION
Lack of randomized placebo-controlled studies and heterogenicity in study design hampers generalized statements about the effects of COCs on sexual function. Despite these challenges, consideration of sexual dysfunction when presenting and prescribing hormonal contraception is essential for informed consent, shared decision making, and ensuring reliable contraceptive choices.
Topics: Humans; Female; Contraceptives, Oral, Combined; Estrogens; Progestins; Sexuality; Orgasm; Libido; Sexual Behavior
PubMed: 38515302
DOI: 10.1093/sxmrev/qeae011 -
Obstetrics and Gynecology May 2024Recurrent pregnancy loss (RPL) affects approximately 5% of couples. Although RPL definitions vary across professional societies, an evaluation after a second clinically...
Recurrent pregnancy loss (RPL) affects approximately 5% of couples. Although RPL definitions vary across professional societies, an evaluation after a second clinically recognized first-trimester pregnancy loss is recommended. Good quality evidence links parental chromosomal rearrangements, uterine anomalies, and antiphospholipid syndrome (APS) to RPL. In contrast, the relationship between RPL and other endocrine, hematologic, and immunologic disorders or environmental exposures is less clear. Anticoagulant therapy and low-dose aspirin are recommended for patients with RPL who have also been diagnosed with APS. Vaginal progesterone supplementation may be considered in patients experiencing vaginal bleeding during the first trimester. Surgical correction may be considered for patients with RPL in whom a uterine anomaly is identified. Evaluation and management of additional comorbidities should be guided by the patient's history rather than solely based on the diagnosis of RPL, with the goal of improving overall health to reduce complications in the event of pregnancy. Most people with RPL, including those without identifiable risk factors, are expected to achieve a live birth within 5 years from the initial evaluation. Nevertheless, clinicians should be sensitive to the psychological needs of individuals with this condition and provide compassionate and supportive care across all stages.
Topics: Pregnancy; Female; Humans; Abortion, Habitual; Chromosome Aberrations; Pregnancy Trimester, First; Antiphospholipid Syndrome; Progesterone; Urogenital Abnormalities; Uterus
PubMed: 38176012
DOI: 10.1097/AOG.0000000000005498 -
Current Opinion in Obstetrics &... Jun 2024This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published... (Review)
Review
PURPOSE OF REVIEW
This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published research on different endometrial preparation methods for frozen embryo transfer (FET).
RECENT FINDINGS
While the artificial-FET cycle provides advantages in scheduling and implantation, it falls short in ensuring optimal obstetric outcomes. In contrast, natural-FET ensures embryo implantation conditions if ovulation is correctly identified. Supplementing with exogenous progesterone shields against low corpus luteum progesterone secretion, crucial for positive obstetric outcomes. In mNC-FET, ovulation is hCG-triggered, closely resembling natural cycles and reducing monitoring visits for enhanced patient convenience.Letrozole is a recommended option for anovulatory patients, preserving endometrial thickness. It is cost-effective, less likely to induce multifollicular development than gonadotropins, and better tolerated.In a novel approach, the natural-proliferative-phase-FET initiates progesterone in an unmediated ovulatory cycle at 7 mm endometrial thickness, combining the benefits of a natural proliferative endometrium with the convenience of scheduled artificial cycles.
SUMMARY
The artificial cycle offers scheduling advantages, but may compromise obstetric outcomes. Natural FET relies on accurate ovulation timing for successful implantation. mNC-FET simplifies the process using hCG induction, minimizing clinic visits for improved convenience. Letrozole is highlighted as a cost-effective and well tolerated option in anovulatory patients. A recent innovative approach combines elements of natural and artificial cycles, showing promise for FET procedures.
Topics: Humans; Female; Embryo Transfer; Pregnancy; Cryopreservation; Embryo Implantation; Progesterone; Endometrium; Ovulation Induction; Letrozole; Fertilization in Vitro; Pregnancy Rate
PubMed: 38295043
DOI: 10.1097/GCO.0000000000000943 -
Sleep Medicine Clinics Dec 2023Aspects of sleep change across the menstrual cycle in some women. Poorer sleep quality in the premenstrual phase and menstruation is common in women with premenstrual... (Review)
Review
Aspects of sleep change across the menstrual cycle in some women. Poorer sleep quality in the premenstrual phase and menstruation is common in women with premenstrual symptoms or painful menstrual cramps. Although objective sleep continuity remains unchanged across the regular, asymptomatic menstrual cycle, activity in the sleep electroencephalogram varies, with a prominent increase in sleep spindle activity in the postovulatory luteal phase, when progesterone is present, relative to the follicular phase. Menstrual cycle phase, reproductive stage, and menstrual-related disorders should be considered when assessing women's sleep complaints.
Topics: Female; Humans; Menstrual Cycle; Sleep; Progesterone; Menstruation Disturbances; Sleep Initiation and Maintenance Disorders
PubMed: 38501513
DOI: 10.1016/j.jsmc.2023.06.003 -
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 -
European Journal of Obstetrics,... May 2024Endometriosis is a common gynecological disease among women of reproductive age. It is a chronic estrogen and progestin related inflammatory disease. At present, the... (Review)
Review
Endometriosis is a common gynecological disease among women of reproductive age. It is a chronic estrogen and progestin related inflammatory disease. At present, the main treatments for endometriosis are drug therapy and surgery. In drug therapy, progesterone is listed as the first-line recommendation in multinational guidelines. Dydrogesterone, as an oral reversal progesterone, can slow down the metabolism of progesterone, inhibit angiogenesis and extracellular matrix degradation to inhibit the proliferation of the ectopic endometrium, induce the atrophy of the ectopic endometrium through the pro-apoptotic pathway, and treat endometriosis through multiple mechanisms of regulating inflammatory factors to reduce inflammation. Clinically, dydrogesterone treatment of endometriosis can relieve patients' symptoms, promote fertility, be used in combination, and is safe. This article will review the mechanism and clinical application of dydrogesterone in the treatment of endometriosis.
Topics: Humans; Female; Dydrogesterone; Progesterone; Endometriosis; Progestins; Endometrium
PubMed: 38430648
DOI: 10.1016/j.ejogrb.2024.02.034