A 19-year-old woman had stage IA endometrial carcinoma treated with medroxyprogesterone acetate and experienced a recurrence. This patient\'s experience illustrates the importance of a thorough history and endometrial assessment in younger patients.

To assess the risk of intracranial meningioma associated with the use of selected progestogens.
National case-control study.
French National Health Data System (ie, Système National des Données de Santé).
Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls).
Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association.
Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) v 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) v 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) v 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) v 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) v 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) v 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use.
Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.

Progestin therapy is a fertility-sparing treatment option for well-differentiated stage IA endometrioid carcinomas without myometrial invasion. Here, we present a case of successful pregnancy and live birth following long-term progestin therapy in a patient with stage II well-differentiated endometrioid carcinoma. A 30-year-old nulliparous woman with an unremarkable medical history presented with abnormal uterine bleeding. A 45 mm mass was identified in the lower uterine segment. An endometrial biopsy revealed grade 1 endometrioid carcinoma, leading to a diagnosis of stage II uterine corpus cancer based on hysteroscopic findings. The patient refused surgical treatment and underwent oocyte retrieval and cryopreservation at another hospital. A subsequent endometrial biopsy revealed a marked reduction in the Ki-67 index from approximately 60 % to less than 10 %, suggesting the possibility of a hormone-sensitive tumor. The patient persistently refused surgery. Therefore, progestin therapy with medroxyprogesterone acetate (MPA) at a dose of 400 mg/day was initiated as a temporary measure until the patient would accept surgery. The tumor gradually reduced in size and eventually disappeared after 9 months. The MPA therapy was discontinued uneventfully after 20 months. Sixteen months after the discontinuation of MPA therapy, atypical endometrial hyperplasia was detected, and a second round of MPA therapy was initiated. Progestin retreatment was successful and was discontinued at 6 months. Four years after the initial treatment, the patient achieved pregnancy through timed intercourse and delivered a healthy baby at 38 weeks of gestation.

BACKGROUND: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples.
METHODS: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance.
RESULTS: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab.
CONCLUSIONS: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended.

BACKGROUND: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future.
METHODS: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far.
CONCLUSIONS: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy.

OBJECTIVE: To assess the associations between depot medroxyprogesterone acetate (DMPA) and endometrial cancer.
METHODS: This multicenter case-control study was conducted among tertiary hospitals in Thailand. Patients were women with endometrial cancer. Controls were women admitted for other conditions, matched for age within 5 years of the patients\' age. The controls had to have no abnormal vaginal bleeding, history of hysterectomy, or cancers of the other organs. A standardized questionnaire was used to gather information. Conditional logistic regression was applied to calculate adjusted odds ratio (aORs) and 95% confidence intervals (CIs).
RESULTS: During 2015 to 2021, 378 patients and 1134 controls were included. Ever use of DMPA was associated with a 70% decreased overall risk of endometrial cancer (aOR, 0.30 [95% CI, 0.21-0.42]). Endometrial cancer risk declined by 3% (aOR, 0.97 [95% CI, 0.96-0.98]) for every 3 months of DMPA use. The magnitude of the decline in endometrial cancer risk did not vary appreciably by cancer subtypes (aOR, 0.26 [95% CI, 0.17-0.41] and 0.38 [95% CI, 0.22-0.65] for low-grade and high-grade tumors, respectively).
CONCLUSIONS: Depot medroxyprogesterone acetate use was inversely associated with endometrial cancer risk in a duration-dependent manner. This association was independent of cancer subtype.

UNASSIGNED: Although non-barrier contraception is commonly prescribed, the risk of urinary tract infections (UTI) with contraceptive exposure is unclear.
UNASSIGNED: Using data from Vanderbilt University Medical Centre\'s deidentified electronic health record (EHR), women ages 18-52 were randomly sampled and matched based on age and length of EHR. This case-control analysis tested for association between contraception exposure and outcome using UTI-positive (UTI+) as cases and upper respiratory infection+ (URI+) as controls.
UNASSIGNED: 24,563 UTI + cases (mean EHR: 64.2 months; mean age: 31.2 years) and 48,649 UTI-/URI + controls (mean EHR: 63.2 months; mean age: 31.9 years) were analysed. In the primary analysis, UTI risk was statistically significantly increased for the oral contraceptive pill (OCP; OR = 1.10 [95%CI = 1.02-1.11], p ≤ 0.05), intrauterine device (IUD; OR = 1.13 [95%CI = 1.04-1.23], p ≤ 0.05), etonogestrel implant (Nexplanon®; OR = 1.56 [95% CI = 1.24-1.96], p ≤ 0.05), and medroxyprogesterone acetate injectable (Depo-Provera®; OR = 2.16 [95%CI = 1.99-2.33], p ≤ 0.05) use compared to women not prescribed contraception. A secondary analysis that included any non-IUD contraception, which could serve as a proxy for sexual activity, demonstrated a small attenuation for the association between UTI and IUD (OR = 1.09 [95%CI = 0.98-1.21], p = 0.13).
UNASSIGNED: This study notes potential for a small increase in UTIs with contraceptive use. Prospective studies are required before this information is applied in clinical settings.
UNASSIGNED: Although non-barrier contraception is commonly prescribed, the risk of urinary tract infections (UTI) with contraceptive exposure is poorly understood. This large-cohort, case-control study notes potential for a small increase in UTIs with contraceptive use.

BACKGROUND: Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed.
METHODS: This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018.
RESULTS: We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed.
CONCLUSIONS: This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.

Pharmacological regimens with multiple medications are being used in fertility treatments. Herein, we report a case of a 40-year-old Japanese woman who developed Stevens-Johnson syndrome (SJS) with a severe ocular complication during fertility treatment. Despite early multimodal interventions, including methylprednisolone pulse therapy and plasma exchange, her ocular complications persisted for more than a year. The four drugs administered in this case (cabergoline, medroxyprogesterone acetate, clomiphene, and intravenous human chorionic gonadotropin) have never been reported to induce SJS. Based on this case, we suggest that obstetricians, gynecologists, and dermatologists should be aware of fertility treatment-induced severe drug eruptions.

BACKGROUND: Endometrial mesonephric-like adenocarcinomas exhibit classical histologic features of mesonephric carcinoma; however, it remains unclear whether these tumors represent mesonephric (Wolffian) carcinoma or endometrioid (Müllerian) carcinomas that closely mimic mesonephric carcinoma.
METHODS: A 32-year-old Japanese primigravida presented with atypical vaginal bleeding. An endometrial biopsy suggested low-grade endometrioid carcinoma, and she was administered medroxyprogesterone acetate. Her tumor recurred 6 years later, and she underwent hysterectomy, salpingo-oophorectomy, and omentectomy, at which point she was diagnosed with mesonephric-like adenocarcinoma of the uterine endometrium. Retrospective pathological review of the initial biopsy confirmed coexisting low-grade endometrioid carcinoma and mesonephric-like adenocarcinoma of the uterine endometrium. On immunohistochemistry, the endometrioid carcinoma component was diffuse positive for estrogen and progesterone receptors but negative for thyroid transcription factor 1. However, the mesonephric-like adenocarcinoma component exhibited a mixture of estrogen receptor- and thyroid transcription factor 1-positive cells within the same glands.
CONCLUSIONS: We encountered a patient with coexisting endometrial mesonephric-like adenocarcinoma and low-grade endometrioid carcinoma, which was treated using medroxyprogesterone acetate therapy, resulting in recurrence of mesonephric-like adenocarcinoma alone. These clinicopathological findings support the prevailing notions that mesonephric-like adenocarcinoma is a Müllerian adenocarcinoma exhibiting mesonephric differentiation.