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Immunity Nov 2023Immune responses to antigens, including innocuous, self, tumor, microbial, and vaccine antigens, differ between males and females. The quest to uncover the mechanisms... (Review)
Review
Immune responses to antigens, including innocuous, self, tumor, microbial, and vaccine antigens, differ between males and females. The quest to uncover the mechanisms for biological sex differences in the immune system has intensified, with considerable literature pointing toward sex hormonal influences on immune cell function. Sex steroids, including estrogens, androgens, and progestins, have profound effects on immune function. As such, drastic changes in sex steroid concentrations that occur with aging (e.g., after puberty or during the menopause transition) or pregnancy impact immune responses and the pathogenesis of immune-related diseases. The effect of sex steroids on immunity involves both the concentration of the ligand and the density and distribution of genomic and nongenomic receptors that serve as transcriptional regulators of immune cellular responses to affect autoimmunity, allergy, infectious diseases, cancers, and responses to vaccines. The next frontier will be harnessing these effects of sex steroids to improve therapeutic outcomes.
Topics: Pregnancy; Female; Male; Humans; Gonadal Steroid Hormones; Estrogens; Progestins; Androgens; Neoplasms; Steroids; Immunity; Sex Characteristics
PubMed: 37967530
DOI: 10.1016/j.immuni.2023.10.008 -
The Journal of Allergy and Clinical... Dec 2023Progestogen hypersensitivity (PH) is a heterogeneous disease characterized by diverse cutaneous manifestations, bronchospasm, and/or anaphylaxis. Possible triggers...
Progestogen hypersensitivity (PH) is a heterogeneous disease characterized by diverse cutaneous manifestations, bronchospasm, and/or anaphylaxis. Possible triggers include ovarian progesterone and exogenous progestogens. The timing of symptoms is critical to diagnose PH: during the luteal phase of the menstrual cycle for the endogenous form and after exposure to progestins for exogenous PH. Diagnostic modalities such as progesterone skin testing have low sensitivity and specificity for PH. When exogenous PH is suspected, the allergist should consider a progestogen challenge. Treatment strategies should be tailored for each patient, including symptom-directed therapies, ovulation suppression, and progesterone desensitization. Future studies should explore the mechanisms of PH, validation of diagnostic criteria, and standardization of treatment strategies.
Topics: Female; Humans; Progestins; Progesterone; Desensitization, Immunologic; Anaphylaxis; Menstrual Cycle
PubMed: 37579875
DOI: 10.1016/j.jaip.2023.07.050 -
Menopause (New York, N.Y.) May 2024The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of...
OBJECTIVES
The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths.
METHODS
Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia.
RESULTS
Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%).
CONCLUSIONS
Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.
Topics: Humans; Female; Aged; Estrogen Replacement Therapy; United States; Women's Health; Progestins; Menopause; Cardiovascular Diseases; Medicare; Estrogens; Aged, 80 and over; Neoplasms; Dementia; Proportional Hazards Models
PubMed: 38595196
DOI: 10.1097/GME.0000000000002335 -
Drugs Nov 2023Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on... (Review)
Review
Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Topics: Female; Humans; Adenomyosis; Quality of Life; Uterus; Progestins; Gonadotropin-Releasing Hormone; Levonorgestrel
PubMed: 37837497
DOI: 10.1007/s40265-023-01957-7 -
Nature Reviews. Endocrinology Mar 2024Infertility affects one in six couples, with in vitro fertilization (IVF) offering many the chance of conception. Compared to the solitary oocyte produced during the... (Review)
Review
Infertility affects one in six couples, with in vitro fertilization (IVF) offering many the chance of conception. Compared to the solitary oocyte produced during the natural menstrual cycle, the supraphysiological ovarian stimulation needed to produce multiple oocytes during IVF results in a dysfunctional luteal phase that can be insufficient to support implantation and maintain pregnancy. Consequently, hormonal supplementation with luteal phase support, principally exogenous progesterone, is used to optimize pregnancy rates; however, luteal phase support remains largely 'black-box' with insufficient clarity regarding the optimal timing, dosing, route and duration of treatment. Herein, we review the evidence on luteal phase support and highlight remaining uncertainties and future research directions. Specifically, we outline the physiological luteal phase, which is regulated by progesterone from the corpus luteum, and evaluate how it is altered by the supraphysiological ovarian stimulation used during IVF. Additionally, we describe the effects of the hormonal triggers used to mature oocytes on the degree of luteal phase support required. We explain the histological transformation of the endometrium during the luteal phase and evaluate markers of endometrial receptivity that attempt to identify the 'window of implantation'. We also cover progesterone receptor signalling, circulating progesterone levels associated with implantation, and the pharmacokinetics of available progesterone formulations to inform the design of luteal phase support regimens.
Topics: Pregnancy; Female; Humans; Progesterone; Luteal Phase; Chorionic Gonadotropin; Reproductive Techniques, Assisted; Fertilization in Vitro; Ovulation Induction
PubMed: 38110672
DOI: 10.1038/s41574-023-00921-5