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American Journal of Cancer Research 2024Adrenocortical carcinoma (ACC) is a malignant tumour that originates from the adrenal cortex. It is a highly aggressive cancer characterised by a poor prognosis with an... (Review)
Review
The effect of adjuvant mitotane therapy of the adrenocortical carcinoma on the endometrium and its clinical consequences in menstruating women. Literature review and authors' own experiences.
Adrenocortical carcinoma (ACC) is a malignant tumour that originates from the adrenal cortex. It is a highly aggressive cancer characterised by a poor prognosis with an annual incidence estimated to be up to 2 cases per million. In the adult population, ACC is diagnosed typically between 40 and 50 years of age, more often in women. Complete surgical resection of the tumour is the primary treatment method for ACC. Unfortunately, despite properly performed adrenalectomy, regional recurrences or distant metastases are detected in up to 90% of the patients. For that reason, adjuvant therapy is recommended. Mitotane is the most effective adrenal-specific agent used in adjuvant and palliative therapy. Two menstruating patients, after adrenalectomy due to ACC, during adjuvant mitotane therapy, have been included in the study. The study aimed to assess the effect of mitotane therapy on the endometrium and its clinical consequences, based on the analysis of these two cases and a review of the literature. It seems that menorrhagia may be expected during adjuvant mitotane therapy of ACC in menstruating women. Heavy uterine bleeding during menstruation may appear several months after the beginning of therapy. The likely mechanism for heavy menstrual bleeding is complex. Menorrhagia can occur due to the toxic effect of mitotane in the form of a haemorrhagic diathesis, while long-term treatment (over ten months) can lead to relative hypoestrogenism resulting in endometrial hyperplasia. Clinical signs of hypoestrogenism during mitotane treatment, have been described (including pre-puberty girls) and should be considered as a side-effect of the therapy. Menorrhagia may lead to severe anaemia, so this should be considered when planning mitotane treatment. Continuous gestagen therapy is helpful in the treatment of the above disorders. After over 60 years of experience with mitotane usage, knowledge about it is still insufficient, and further studies are required.
PubMed: 38726272
DOI: 10.62347/QKWF9884 -
American Journal of Obstetrics and... Dec 2023In the pivotal LIBERTY 1 and 2 trials and long-term extension study, once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the pivotal LIBERTY 1 and 2 trials and long-term extension study, once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) reduced menstrual blood loss volume and pain among women with uterine fibroids. Relugolix combination therapy was well tolerated with preservation of bone mineral density through 52 weeks.
OBJECTIVE
This study aimed to report the 2-year relugolix combination therapy efficacy and safety results of the phase 3 LIBERTY randomized withdrawal study.
STUDY DESIGN
Women with uterine fibroid-associated heavy menstrual bleeding who completed the 24-week LIBERTY 1 or 2 trials, followed by the 28-week long-term extension study (up to 52 weeks total treatment), and who met the responder criteria (menstrual blood loss volume <80 mL and ≥50% reduction from pivotal study baseline at week 48 [week 24 of long-term extension]) were randomized in a 1:1 ratio to either blinded treatment with relugolix combination therapy or placebo for 52 weeks (total treatment period, 104 weeks). For women who had a relapse of heavy menstrual bleeding during the study (menstrual blood loss volume ≥80 mL), open-label relugolix combination therapy was offered. The primary endpoint was the proportion of women who maintained menstrual blood loss volume <80 mL through week 76 (week 24 of randomized withdrawal study). Secondary endpoints included time to menstrual blood loss volume ≥80 mL, proportion of women who maintained a menstrual blood loss volume of <80 mL through week 104 (over the 52-week randomized treatment period), the proportion of women who achieved or maintained amenorrhea at week 76 at the end of treatment, and the change in Uterine Fibroid Symptom-Quality of Life Bleeding and Pelvic Discomfort Scale and symptom severity scores. Analyses were performed for the modified intent-to-treat population, including all randomized women who received ≥1 dose of the study drug.
RESULTS
Of the 229 randomized women (relugolix combination therapy, n=115; placebo, n=114), 228 received the study drug and 175 (76.7%) completed the randomized withdrawal study. Through week 76, 78.4% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 15.1% in the placebo group (difference, 63.4%; 95% confidence interval, 52.9%-73.9%; P<.0001). At week 104, 69.8% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 11.8% in the placebo group (difference, 58.0%; 95% confidence interval, 47.0%-69.1%; P<.0001). Through week 104, 88.3% of women on placebo relapsed with heavy menstrual bleeding (median time to relapse, 5.9 weeks). Among the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 women responded to relugolix combination therapy with a menstrual blood loss volume <80 mL. The proportion of women who achieved or maintained amenorrhea were 57.4% vs 13.3% at week 76 (difference, 44.1%; 95% confidence interval, 33.10%-55.1%; P<.0001) and 58.3% vs 10.6% at week 104 (difference, 47.6%; 95% confidence interval, 37.0%-58.3%; nominal P<.0001) for relugolix combination therapy and the placebo group, respectively. Relugolix combination therapy was generally well tolerated; no new safety signals were identified, and the adverse event profile over the second year was consistent with that reported through the first year of treatment. Bone mineral density remained stable in women who received relugolix combination therapy from week 52 to week 104. In women continuously treated with relugolix combination therapy up to 2 years, bone mineral density was generally preserved.
CONCLUSION
After 2 years of treatment with relugolix combination therapy, there was evidence of durability of the effect in maintaining low menstrual blood loss volume in women with symptomatic uterine fibroids. Most women had return of heavy menstrual bleeding and associated symptoms after treatment cessation, which improved upon retreatment with relugolix combination therapy. Relugolix combination therapy was well tolerated, the adverse event profile remained consistent, and the mean bone mineral density was generally preserved through 2 years of treatment.
Topics: Female; Humans; Menorrhagia; Uterine Neoplasms; Amenorrhea; Quality of Life; Neoplasm Recurrence, Local; Leiomyoma; Uterine Hemorrhage; Recurrence
PubMed: 37666383
DOI: 10.1016/j.ajog.2023.08.030 -
Clinical Cancer Research : An Official... Mar 2024Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβ receptor II (a TGFβ "trap") fused to a human IgG1 mAb...
PURPOSE
Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβ receptor II (a TGFβ "trap") fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer.
PATIENTS AND METHODS
In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n = 8) or without (Cohort 1B; n = 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n = 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics.
RESULTS
At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1-2 in severity, most commonly anemia (62.5%-77.8%) and bleeding events (62.5%-77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9-96.8], 44.4% (95% CI, 13.7-78.8), and 62.5% (95% CI, 24.5-91.5) in Cohorts 1A, 1B, and 2, respectively.
CONCLUSIONS
Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFβ/PD-L1 inhibition in human papillomavirus-associated cancers, including cervical cancer.
Topics: Female; Humans; Uterine Cervical Neoplasms; B7-H1 Antigen; Cisplatin; Neoplasm Recurrence, Local; Immunologic Factors; Paclitaxel; Transforming Growth Factor beta
PubMed: 38165683
DOI: 10.1158/1078-0432.CCR-23-1829 -
Cureus Apr 2024Adolescence is a crucial phase in a woman's life, as it signifies the beginning of her reproductive journey. During this time, there are notable variations in sexual...
BACKGROUND AND OBJECTIVES
Adolescence is a crucial phase in a woman's life, as it signifies the beginning of her reproductive journey. During this time, there are notable variations in sexual development and a sense of caution that can present challenges for healthcare providers. The rationale for studying adolescent gynecological problems lies in the need to understand and address the unique reproductive health challenges faced by young girls. By investigating these issues, researchers and healthcare professionals can develop effective strategies for prevention, early detection, and treatment of gynecological conditions in adolescents. This knowledge is crucial for promoting the overall well-being and reproductive health of young girls, ensuring they receive appropriate care and support during this critical stage of development. This study focuses on identifying the most common gynecological issues in teenagers, exploring the root causes, examining the available treatment options, and understanding how they are managed at a tertiary care facility. Methods: This cross-sectional observational study took place at a tertiary care center and focused on gynecological issues in adolescent females who sought care at the gynecology department from January 2016 to December 2022. The study participants were categorized into three groups: early adolescence (10-13 years), middle adolescence (14-16 years), and late adolescence (17-19 years) for analysis. Ethical approval was obtained for this hospital-based research, which involved examining, investigating, and treating the study participants.
RESULTS
Out of the 49,700 new female patients, 2000 (4.02%) fell within the specified age range. The average age of the participants was 16.87±2.16, and the majority of them sought help for menstrual issues (63.45%), followed by abdominal discomfort (15.6%) and vaginal discharge (7.2%). Menstrual disorders were the most common concern, with dysmenorrhea and puberty menorrhagia being prevalent issues. Abdominal pain was caused by various factors, such as urinary tract infections, ovarian tumors, pelvic inflammatory disease, endometriosis, and endometrial tuberculosis. The majority of cases were treated conservatively, with only a small percentage requiring surgical intervention.
CONCLUSION
The significance of early detection and intervention in addressing gynecological issues among adolescents is highlighted in the findings of this research, underscoring the necessity for specialized healthcare services that cater to the specific needs of this demographic. Adolescent gynecology plays a crucial role in safeguarding the reproductive health and overall well-being of young women, emphasizing the importance of seeking assistance proactively.
PubMed: 38711716
DOI: 10.7759/cureus.57713 -
BMC Women's Health Dec 2023Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these...
BACKGROUND
Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these racial differences. In the U.S., electronic medical records (EMR) data can offer richer detail on factors driving surgical decision-making among reproductive-aged populations than insurance claims-based data. Our objective in this cohort profile paper is to describe the Carolina Hysterectomy Cohort (CHC), a large EMR-based case-series of premenopausal hysterectomy patients in the U.S. South, supplemented with census and surgeon licensing data. To demonstrate one strength of the data, we evaluate whether patient and surgeon characteristics differ by insurance payor type.
METHODS
We used structured and abstracted EMR data to identify and characterize patients aged 18-44 years who received hysterectomies for non-cancerous conditions between 10/02/2014-12/31/2017 in a large health care system comprised of 10 hospitals in North Carolina. We used Chi-squared and Kruskal Wallis tests to compare whether patients' socio-demographic and relevant clinical characteristics, and surgeon characteristics differed by patient insurance payor (public, private, uninsured).
RESULTS
Of 1857 patients (including 55% non-Hispanic White, 30% non-Hispanic Black, 9% Hispanic), 75% were privately-insured, 17% were publicly-insured, and 7% were uninsured. Menorrhagia was more prevalent among the publicly-insured (74% vs 68% overall). Fibroids were more prevalent among the privately-insured (62%) and the uninsured (68%). Most privately insured patients were treated at non-academic hospitals (65%) whereas most publicly insured and uninsured patients were treated at academic centers (66 and 86%, respectively). Publicly insured and uninsured patients had higher median bleeding (public: 7.0, uninsured: 9.0, private: 5.0) and pain (public: 6.0, uninsured: 6.0, private: 3.0) symptom scores than the privately insured. There were no statistical differences in surgeon characteristics by payor groups.
CONCLUSION
This novel study design, a large EMR-based case series of hysterectomies linked to physician licensing data and manually abstracted data from unstructured clinical notes, enabled identification and characterization of a diverse reproductive-aged patient population more comprehensively than claims data would allow. In subsequent phases of this research, the CHC will leverage these rich clinical data to investigate multilevel drivers of hysterectomy in an ethnoracially, economically, and clinically diverse series of hysterectomy patients.
Topics: Female; Humans; United States; Adult; Insurance Coverage; Medically Uninsured; Hospitals; Surgeons; Hysterectomy; Insurance, Health
PubMed: 38114962
DOI: 10.1186/s12905-023-02837-8 -
Cureus Apr 2024Introduction Menstrual changes after COVID-19 vaccination suggest a secondary connection to the immune response to vaccination rather than a specific component of the...
Introduction Menstrual changes after COVID-19 vaccination suggest a secondary connection to the immune response to vaccination rather than a specific component of the vaccine. The evaluation of these alterations in women with the same and multiple vaccination schedules will provide valuable information. Methods An observational, cross-sectional study was carried out; data were collected through a survey of 164 vaccinated women at the American British Cowdray (ABC) Santa Fe Medical Center Hospital in Mexico City. The survey was validated by the Delphi method. Results The survey was applied from March 2023 to February 2024. Post-vaccination menstrual alterations occurred in 48.1%; the most frequent alteration was menorrhagia in 20.7% and pain accompanied by menstruation in 27.4%. Fifty-seven percent had a history of previous COVID-19 infection. There were no significant associations between changes in menstrual bleeding after vaccination, history of COVID-19 infection, and age group (p>0.9). However, women who received multiple doses of vaccines had a higher risk of suffering abnormalities in bleeding by 36.6%. Conclusion The incidence of menstrual disorders in this study post COVID-19 vaccination was 49%. Menstrual alterations in patients who received multiple doses and a single regimen were similar at 47% and 48%, where there is no statistical significance. The greatest number of menstrual alterations was seen in the first dose at 36%, probably due to the immunity they acquired after the different types of vaccination. Vaccination is a very effective way to prevent the severity of COVID-19 infection; it has an impact on menstrual bleeding in terms of menorrhagia and metrorrhagia. Vaccination against COVID-19 is associated with small changes in the menstrual cycle, without statistical significance. Women receiving the first dose of the vaccine had changes in the amount of bleeding specifically the amount.
PubMed: 38654961
DOI: 10.7759/cureus.58783 -
SAGE Open Medicine 2024Uterine fibroids are the commonest benign tumors of the reproductive tract in women of childbearing age. They are usually asymptomatic but can cause menorrhagia.... (Review)
Review
INTRODUCTION
Uterine fibroids are the commonest benign tumors of the reproductive tract in women of childbearing age. They are usually asymptomatic but can cause menorrhagia. Treatments include myomectomy and uterine artery embolization (UAE). The latter is a relatively new procedure, therefore of special interest.
OBJECTIVES
We conducted a systematic review and meta-analysis of all published studies to provide a comprehensive outlook on the effectiveness of UAE by comparing its outcomes to those of myomectomy. Electronic databases (PubMed and Cochrane Central) were systematically searched from January 2000 to March 2022 for published randomized control trials, observational studies, and meta-analyses that compared UAE to myomectomy for at least one of the pre-specified outcomes, namely re-intervention rates, length of hospital stay, and complications.
METHODS
We shortlisted nine studies for the final analysis. For continuous outcomes, results from random-effects meta-analysis were presented as mean differences (MDs) and corresponding 95% confidence intervals (CIs). Risk ratios (RRs) for dichotomous outcomes were pooled using a random-effects model.
RESULTS
The final analysis consisted of nine studies. Factors like re-intervention, hospitalization, and complications, each with its unique follow-up duration were assessed. Pooled analysis demonstrated significant results for greater re-intervention rates with UAE as compared to myomectomy (RR: 2.16, 95% CI: (1.27-3.66), value 0.004, heterogeneity = 85%). UAE holds a greater but statistically insignificant risk for major complications (RR: 0.62, 95% CI: (0.29-1.33), value 0.22, heterogeneity = 0%) and myomectomy shows a statistically insignificant greater risk for minor complications (RR: 1.72, 95% CI: (0.92-3.22), value 0.09, heterogeneity = 0%). UAE had a shorter but statistically insignificant duration of hospital stay (MD: -1.12, 95% CI: (-2.50 to 0.27), value 0.11, heterogeneity = 96%) (value for subgroup differences = 0.005).
CONCLUSION
Our meta-analysis of approximately 196,595 patients demonstrates that myomectomy results in a significant reduction in re-intervention rate compared to UAE.
PubMed: 38751568
DOI: 10.1177/20503121241236141 -
Korean Journal of Anesthesiology Aug 2023Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that has been used for several decades to reduce blood loss during surgery and after trauma. TXA was...
Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that has been used for several decades to reduce blood loss during surgery and after trauma. TXA was traditionally used to reduce bleeding in various clinical settings such as menorrhagia, hemophilia, or other bleeding disorder . Numerous studies have demonstrated the efficacy of TXA in reducing blood loss and the need for transfusions. Interest in the potential applications of TXA beyond its traditional use has been growing recently, with studies investigating the use of TXA in postpartum hemorrhage, cardiac surgery, trauma, neurosurgery, and orthopedic surgery. Despite its widespread use and expanding indications, data regarding the safe and appropriate use of TXA is lacking. Recent clinical trials have found various potential risks and limitations in the long-term benefits of TXA. This narrative review summarizes the clinical applications and limitations of TXA.
PubMed: 37599607
DOI: 10.4097/kja.23530 -
Journal of Pediatric and Adolescent... Apr 2024The aim of this review was to create an overview of available instruments used to evaluate the menstrual complaints of dysmenorrhea and heavy menstrual bleeding (HMB) in... (Review)
Review
STUDY OBJECTIVE
The aim of this review was to create an overview of available instruments used to evaluate the menstrual complaints of dysmenorrhea and heavy menstrual bleeding (HMB) in adolescents.
METHODS
The search was conducted in PubMed, Web of Science, Embase, and PsycINFO on December 1, 2022. Studies published in English reporting on menstrual complaints among girls aged 10-19 were included. The quality and bias risk was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2.
RESULTS
Of 8994 identified studies, 57 were included. In these studies, 19 instruments were described, of which 8 were validated in adolescents. One was difficult to use in daily practice, 1 had low sensitivity and specificity in the detection of HMB, 2 were validated by face validity, and 2 were not specifically developed to evaluate (the impact of) menstrual complaints. Therefore, only 2 were validated and feasible to measure adolescent menstrual complaints: the Period ImPact and Pain Assessment (PIPPA) and the Adolescent Menstrual Bleeding Questionnaire (aMBQ). Remarkably, the Pictorial Blood Loss Assessment Chart (PBAC) was the most frequently used instrument in adolescents. There was one modified version of the PBAC for adolescents, which had a lower cutoff value for HMB and low sensitivity and specificity.
CONCLUSION
We found that the PIPPA and aMBQ are suitable for assessing menstrual complaints and their impact on daily activities and health-related quality of life in adolescents. The PBAC, which is used frequently in adults, needs to be further assessed specifically for adolescents. In particular, the clinical relevance of the PBAC cutoff value for HMB should be determined for this age group. Considering the different interpretations, experiences, and limited knowledge of menstrual complaints, instruments suitable for adults may not be suitable for adolescents.
Topics: Adult; Female; Adolescent; Humans; Quality of Life; Menorrhagia; Sensitivity and Specificity; Menstruation; Dysmenorrhea
PubMed: 38104798
DOI: 10.1016/j.jpag.2023.11.011 -
Medicina (Kaunas, Lithuania) Jan 2024: Menstrual changes, including altered cycle length and bleeding patterns, have been reported following COVID-19 vaccination. This study aimed to determine the...
: Menstrual changes, including altered cycle length and bleeding patterns, have been reported following COVID-19 vaccination. This study aimed to determine the prevalence and types of menstrual changes occurring after COVID-19 vaccination among female students and staff at a university in Saudi Arabia. : A cross-sectional study was conducted among women aged 18-39 years who received at least one dose of a COVID-19 vaccine. Eligible participants, including university students and staff, were recruited between May 2022 and November 2022. Participants completed a questionnaire detailing their sociodemographic characteristics, general medical and reproductive history, and menstrual characteristics before and after vaccination. The prevalence of various menstrual changes (cycle length, bleeding days, flow, and mid-cycle spotting) was calculated. The demographic factors associated with menstrual changes were analyzed using chi-squared tests. : The 472 included participants had a mean age of 20.9 years, and 95.3% were unmarried. Changes in menstrual cycle characteristics after COVID-19 vaccination were reported by 54.7% of respondents overall. The most common change was in cycle length, followed by the number of menstruation days and bleeding flow. Menstrual changes were not associated with age, BMI, occupation, marital status, or medical history. Changes in intermenstrual bleeding were more frequently reported after the third dose of the Pfizer vaccine compared to the Moderna vaccine ( = 0.014). : More than half of the recruited female students and staff reported menstrual changes following COVID-19 vaccination, with altered cycle length being the most common. The potential underlying mechanisms and implications of these menstrual alterations require further investigation. These findings provide evidence of the menstrual side effects of COVID-19 vaccines among women in Saudi Arabia.
Topics: Adult; Female; Humans; Young Adult; COVID-19; COVID-19 Vaccines; Cross-Sectional Studies; Menorrhagia; Menstruation; Vaccination
PubMed: 38399494
DOI: 10.3390/medicina60020206