-
BMC Pregnancy and Childbirth Jun 2024The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent...
Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment.
OBJECTIVE
The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model.
METHODS
Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing.
RESULTS
Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed.
CONCLUSION
Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth.
Topics: Female; Pregnancy; Progesterone; Dysbiosis; Vagina; Placenta; Mice; Humans; Animals; Uterus; Microbiota; Premature Birth; Disease Models, Animal; Progestins
PubMed: 38877443
DOI: 10.1186/s12884-024-06595-9 -
JBRA Assisted Reproduction Jun 2024A new approach to evaluate whether Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone was as effective as using dydrogesterone in suppress LH...
OBJECTIVE
A new approach to evaluate whether Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone was as effective as using dydrogesterone in suppress LH pulse surge in young women under stimulation in an oocyte donor programme.
METHODS
This prospective study included 21 patients aged 19 to 32 years-old stimulated with Elonva® 150, associated or not with Menopur® or Merional® (75 or 150IU) since the beginning of the cycle, plus HMG 150-225IU after the 8th day or just HMG 150-300IU per day. Patients were placed in a PPOS protocol with micronized vaginal progesterone (MVP) 200 mg (Gynpro® Exeltis or Junno Farmoquimica) every 12 hours or dydrogesterone (Duphaston® Abbott) 10 mg every 8 hours from the start of stimulation until the day after the GnRH trigger with Triptorelin 0.2 mg (Gonapeptyl daily®). The primary endpoint was the prevention of untimely LH surge, and secondarily the number of 16 mm follicles, retrieved oocytes and metafase II.
RESULTS
Fourteen oocyte donor patients were prescribed MVP while seven others received dydrogesterone (DYG).The gonadotropin protocols included 04 with Corifollitropin alfa 150 plus HMG since the beginning and complemented after the 7th day, and 17 times of just HMG. There was no diferences in the number of follicles >10≤15mm, ≥16mm or number of metafase II oocytes. There was no untimely LH surge on both groups and no OHSS was developed after the agonist trigger.
CONCLUSIONS
Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone seems to be a compelling choice for preventing premature ovulation without compromising oocyte quality in women undergoing ovarian stimulation.
PubMed: 38875128
DOI: 10.5935/1518-0557.20240045 -
Journal of the Turkish German... Jun 2024Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal...
Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy.
PubMed: 38869053
DOI: 10.4274/jtgga.galenos.2024.2023-11-4 -
Frontiers in Oncology 2024Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH)...
OBJECTIVE
Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC.
METHODS
This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed.
RESULTS
The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment.
CONCLUSION
Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.
PubMed: 38863630
DOI: 10.3389/fonc.2024.1386931 -
The Journal of Headache and Pain Jun 2024Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we...
BACKGROUND
Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology.
METHODS
This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7-14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit.
RESULTS
The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 - 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 - 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 - 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 - 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval.
CONCLUSION
Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.
Topics: Humans; Female; Migraine Disorders; Cross-Sectional Studies; Pituitary Adenylate Cyclase-Activating Polypeptide; Adult; Cohort Studies; Menstrual Cycle; Young Adult; Gonadal Steroid Hormones; Contraceptives, Oral, Combined; Estradiol; Progesterone
PubMed: 38858641
DOI: 10.1186/s10194-024-01804-4 -
Gynecologic Oncology Reports Aug 2024Patients with class 3 obesity (BMI ≥ 40) and significant medical comorbidities with complex atypical hyperplasia (CAH) and early-stage endometrial cancer (EC)...
OBJECTIVES
Patients with class 3 obesity (BMI ≥ 40) and significant medical comorbidities with complex atypical hyperplasia (CAH) and early-stage endometrial cancer (EC) present challenges in standard surgical management. Progestin therapy is an alternative used for patient-centered reasons, including the desire for uterine preservation or because surgery is not a safe option. Our objective was to gain insights into the patient experience when undergoing this treatment approach.
METHODS
We identified and recruited patients who received oral or IUD progesterone in the last 5 years for EC or CAH. We conducted semi-structured phone interviews regarding patients' experience with non-surgical management as well as decision-making factors to start progesterone and weight loss. Interviews were audio-recorded and transcriptions were analyzed for common themes.
RESULTS
A total of 20 interviews were performed. We enrolled nine patients with CAH, eight with grade 1 EC, and three with grade 2 EC. The majority of patients (18/20) were managed with IUD. We identified the following 5 common themes support in diagnostic workup and long-term outcomes, autonomy in care, thoroughness in counseling, emotional impact of diagnosis, and perception of obesity as a defining identity.
CONCLUSION
The themes identified in the present study highlight the challenges and the stigma these patients face. It also demonstrates areas of opportunity in their counseling and care, which will help to build a more effective therapeutic relationship and ultimately lead to greater adherence in care.
PubMed: 38854684
DOI: 10.1016/j.gore.2024.101425 -
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