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Nature Genetics Apr 2024Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the...
Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10 mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.
Topics: Humans; Female; Progestins; Proteogenomics; Antineoplastic Agents, Hormonal; Endometrial Hyperplasia; Fertility Preservation; Retrospective Studies; Carcinoma, Endometrioid; Endometrial Neoplasms
PubMed: 38565644
DOI: 10.1038/s41588-024-01703-z -
Human Reproduction (Oxford, England) Oct 2023
Topics: Humans; Progesterone; Female; Pregnancy; Fertilization in Vitro; Hormone Replacement Therapy
PubMed: 37528050
DOI: 10.1093/humrep/dead153 -
The European Journal of Contraception &... Dec 2023abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical... (Review)
Review
BACKGROUND
abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical treatment are ruled out, clinicians should be able to manage these patients conservatively in the most effective way.
MATERIALS AND METHODS
a search in PubMed/MEDLINE database was conducted in order to find relevant and recent meaningful sources for this narrative review.
RESULTS
LNG-IUS 52 mg is the first-line treatment for non-organic causes. Nevertheless, it could be contraindicated or declined by the patient. Combined oral contraceptives (COC) and progestin-only pills inhibit the hypothalamic-pituitary-ovarian axis, preventing ovulation, and induce endometrial atrophy. Consequently, they are effective in treating AUB. Moreover, brand new pills containing a combination of oestrogens, progestins and GnRH antagonists are now available for the management of AUB related to uterine fibroids.
CONCLUSIONS
In daily clinical practice, oral hormonal therapies are convenient and reversible tools to manage AUB when LNG-IUS 52 mg is contraindicated or turn down by the patient. Many oral hormonal therapies are prescribed to treat AUB, but only a few have been approved with this specific indication, therefore further large well-designed studies are necessary in order to compare the efficacy of different pills for treating AUB.
Topics: Female; Humans; Quality of Life; Progestins; Menorrhagia; Contraceptives, Oral, Combined; Leiomyoma; Uterine Hemorrhage; Levonorgestrel
PubMed: 37955241
DOI: 10.1080/13625187.2023.2270098 -
The Veterinary Clinics of North... Sep 2023Progesterone is a worthwhile addition to the clinical assessment of cycle stage for breeding, elective cesarian delivery, and reproductive management in the bitch if... (Review)
Review
Progesterone is a worthwhile addition to the clinical assessment of cycle stage for breeding, elective cesarian delivery, and reproductive management in the bitch if reliably measured. Clinical decisions based on systemic progesterone concentrations also require the rapid return of results. Most commercially accessible analyses capable of returning results within a day still rely primarily on immunoassays of one kind or another. Point-of-care instruments utilizing similar technology have been developed more recently to enable results to be generated in-house. Repeated monitoring of progesterone on whatever platform can be useful if consistent collection and analysis protocols ensure acceptable precision, accuracy, and repeatability.
Topics: Pregnancy; Female; Animals; Dogs; Progesterone; Reproduction; Cesarean Section
PubMed: 37385875
DOI: 10.1016/j.cvsm.2023.05.007 -
International Journal of Gynaecology... Nov 2023To compare the clinical outcomes and cost-effectiveness of progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone-antagonist (GnRH-A)...
OBJECTIVE
To compare the clinical outcomes and cost-effectiveness of progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone-antagonist (GnRH-A) protocol in fertility preservation (FP) in cancer patients. The stimulation option when patients were in the luteal phase was also explored.
METHODS
This retrospective study analyzed clinical data from 163 patients who underwent FP. The number of retrieved oocytes and vitrified oocytes/embryos, total dose of gonadotropin, duration of stimulation, number of injections, and cost were compared among the PPOS, GnRH-A, and luteal phase stimulation (LPS) groups.
RESULTS
No significant differences were noted in the numbers of retrieved oocytes and vitrified oocytes/embryos among the three groups. In the multiple regression model, age (P = 0.02) and antral follicle count (AFC) (P < 0.001), but not the controlled ovarian stimulation (COS) protocols (P = 0.586), were associated with the number of retrieved oocytes. The number of injections and the cost were all significantly lower in the PPOS and LPS groups than in the GnRH-A group(P < 0.001).
CONCLUSION
PPOS had similar clinical results but was superior medically and economically to GnRH-A. For patients in the luteal phase, LPS was an optional protocol with similar outcomes and costs to PPOS.
Topics: Female; Humans; Progestins; Fertility Preservation; Fertilization in Vitro; Retrospective Studies; Luteal Phase; Cost-Benefit Analysis; Lipopolysaccharides; Ovulation Induction; Hormone Antagonists; Gonadotropin-Releasing Hormone
PubMed: 37265085
DOI: 10.1002/ijgo.14903 -
Gynecologie, Obstetrique, Fertilite &... Jan 2024
Topics: Female; Humans; Contraception; Ethinyl Estradiol
PubMed: 37940046
DOI: 10.1016/j.gofs.2023.11.001 -
Gynecological Endocrinology : the... Dec 2023In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To... (Review)
Review
In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Latin America; Ethinyl Estradiol; Estrogens; Women's Health
PubMed: 37857350
DOI: 10.1080/09513590.2023.2271072 -
American Family Physician Feb 2024Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of...
Abnormal uterine bleeding is a common and bothersome symptom in people using hormonal contraception, and it can lead to discontinuation of reliable methods of contraception and unintended pregnancies. Clinicians should counsel individuals about the potential for abnormal bleeding at initiation of the contraceptive method. After considering and excluding other potential causes of abnormal uterine bleeding, clinicians can offer treatment options specific to each hormonal contraceptive method. This article includes algorithms to help clinicians treat abnormal uterine bleeding in people using levonorgestrel intrauterine devices, depo-medroxyprogesterone acetate, progestin implant, progestin-only pills, and combined hormonal contraception. For patients with levonorgestrel intrauterine devices, physicians should first ensure that the device is correctly placed within the uterus, then consider nonsteroidal anti-inflammatory drugs as a first-line treatment for abnormal uterine bleeding; estradiol can be used if nonsteroidal anti-inflammatory drugs are ineffective. For depo-medroxyprogesterone acetate or progestin implant users, combined oral contraceptives or nonsteroidal anti-inflammatory drugs may be considered. For patients using norethindrone progestin-only pills, changing to drospirenone progesterone-only pills may help reduce the bleeding. In people using combined hormonal contraception, it may be helpful to increase estrogen content from 20 mcg to 35 mcg per day, decrease the hormone-free interval (from seven to four or five days) in people using cyclic contraception, or start a trial of low-dose doxycycline. For continuous combined contraception users, adding a hormone-free interval of four or five days can help regulate bleeding patterns.
Topics: Pregnancy; Female; Humans; Levonorgestrel; Progestins; Medroxyprogesterone Acetate; Hormonal Contraception; Contraception; Uterine Hemorrhage; Anti-Inflammatory Agents; Contraceptives, Oral, Hormonal
PubMed: 38393800
DOI: No ID Found -
Reproductive Biomedicine Online Feb 2024Similar to diabetes and unlike many pathogen-induced diseases, endometriosis is likely a result of maladaptation to the evolutionary heritage of humans. The objective of... (Review)
Review
Similar to diabetes and unlike many pathogen-induced diseases, endometriosis is likely a result of maladaptation to the evolutionary heritage of humans. The objective of this article is to review the literature and improve understanding of the evolutionary factors behind endometriosis, leading to more effective prevention and treatment approaches. In primates, spontaneous decidualization of the endometrium evolved to ensure optimal implantation of a limited number of early embryos, unlike many non-primates which depend on early embryos to induce decidualization and subsequent pregnancy. Spontaneous decidualization results in menstrual bleeding when embryo implantation does not occur, and endometriosis is commonly believed to be caused by retrograde menstruation. Although direct evidence is lacking, it is likely that hunter-gatherer women experienced fewer menstrual periods due to pregnancy shortly after menarche, followed by repeated pregnancies and lactation. However, the mismatch between the evolved uterine physiology and rapid societal changes has led to modern women delaying pregnancy and experiencing numerous menstrual periods, potentially increasing the incidence of endometriosis. The symptoms of endometriosis are often managed by suppressing menstruation through systemic hormonal treatments, but these may have side effects. For patients with a family history of endometriosis or in the early stages of the disease, intrauterine devices releasing progesterone locally could prevent uterine bleeding and the development of endometriosis while preserving fertility and minimizing side effects.
Topics: Pregnancy; Animals; Female; Humans; Endometriosis; Progesterone; Menstruation; Uterine Hemorrhage; Endometrium
PubMed: 38177037
DOI: 10.1016/j.rbmo.2023.103695 -
Expert Opinion on Emerging Drugs Dec 2023Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line... (Review)
Review
INTRODUCTION
Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy.
AREAS COVERED
The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis.
EXPERT OPINION
Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.
Topics: Female; Humans; Endometriosis; Hormone Antagonists; Progestins; Estrogens; Gonadotropin-Releasing Hormone; Clinical Trials, Phase II as Topic
PubMed: 38099328
DOI: 10.1080/14728214.2023.2296080