Primary ovarian insufficiency secondary to chemotherapy with inotuzumab ozogamicin and other agents.

Recent advances in targeted therapy with monoclonal antibodies have significantly improved outcomes for people with cancer, sometimes allowing patients to avoid ovotoxic agents altogether. The current understanding is that monoclonal antibody cancer therapies that are not targeted to ovarian antigens should not impact ovarian reserve or increase the risk of primary ovarian insufficiency (POI). We present a case of rapid onset POI in a 23-year-old patient following chemotherapy for relapse/refractory B-cell acute lymphoblastic leukemia with a monoclonal antibody drug-conjugate, inotuzumab ozogamicin, that targets CD22. She was also treated with intrathecal methotrexate, cytarabine, and vincristine which are typically considered low risk for ovotoxicity. She was ovulatory with an AMH of 1.0 ng/mL prior to treatment and 2 months later was found to have an undetectable AMH. The patient experienced a canceled fertility preservation cycle due to an absent response to gonadotropins during ovarian stimulation. Consideration should be given to potential gonadal effects of monoclonal antibody therapies that may not have previously been explored.

Changes in hair cortisol concentration in intrauterine device initiators: A prospective cohort study.

OBJECTIVES: Prior studies found increased hair cortisol concentration (a surrogate marker for hypothalamic-pituitary-adrenal axis activation) in users of the levonorgestrel intrauterine device (LNG 52 mg IUD). We evaluated change in hair cortisol and psychometric tests in women initiating a copper (CuT380 IUD) or LNG 52 mg IUD. STUDY DESIGN: We prospectively enrolled healthy women initiating an LNG 52 mg IUD or CuT380 IUD. Participants provided hair and blood samples and completed psychometric inventories (Patient Health Questionnaire-9, Positive and Negative Affect Schedule, and Psychological General Well-Being Index) after IUD insertion and at 6 and 12 months. We used liquid chromatography with tandem mass spectrometry to measure hair cortisol concentrations. We compared hair cortisol concentrations and psychometric test changes from baseline to 6 and 12 months using independent two-sample t tests. RESULTS: We enrolled 39 of our targeted 86 participants (LNG 52 mg IUD 26, CuT380 IUD 13). Thirty-eight subjects (LNG 52 mg IUD 25, CuT380 IUD 13) completed 6 months of follow-up. We found no difference between cohorts in the mean change in hair cortisol concentrations at 6 months (LNG 52 mg IUD n = 21 [-0.01 pg/mg (95% CI -1.26, 1.23); CuT380 IUD n = 13 [-1.31 pg/mg (-3.36, 0.73)]). While psychometric inventory results remained within normal ranges, LNG 52 mg IUD users reported a trend toward more favorable changes over time. CONCLUSIONS: We did not find clinically important differences in hair cortisol concentrations following initiation of a CuT380 IUD or LNG 52 mg IUD; psychometric inventories demonstrated no adverse effect of hormonal IUDs on mood. IMPLICATIONS: Our findings of similar hair cortisol concentrations following the initiation of either the LNG 52 mg IUD or CuT380 IUD suggest that hormonal IUDs do not increase cortisol concentrations or alter stress reactivity, and favorable effects on psychometric inventories provide further reassurance that the LNG 52 mg IUD has no adverse impact on mood. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03499379.

Menopause hormone therapy and urinary symptoms: a systematic review.

IMPORTANCE: Urogenital changes associated with menopause are now classified as genitourinary syndrome of menopause (GSM), which includes symptoms of urgency, frequency, dysuria, and recurrent urinary tract infections for which the recommended treatment is estrogen. However, the association between menopause and urinary symptoms and the efficacy of hormone therapy for these symptoms is uncertain. OBJECTIVE: Our objective was to define the relationship between menopause and urinary symptoms including dysuria, urgency, frequency, recurrent urinary tract infections (UTIs), and urge and stress incontinence by conducting a systematic review of the effects of hormone therapy (HT) for urinary symptoms in perimenopausal and postmenopausal women. EVIDENCE REVIEW: Eligible studies included randomized control trials with perimenopausal and postmenopausal women with a primary or secondary outcome of the following urinary symptoms: dysuria, frequent UTI, urgency, frequency, and incontinence, included at least one treatment arm of estrogen therapy, and were in English. Animal trials, cancer studies and pharmacokinetic studies, secondary analyses, and conference abstracts were excluded. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched until April 2022. Two authors reviewed each article with discrepancies resolved through whole group consensus. Data extracted included the following: publication date, country, setting, subject number, follow-up, duration, age, race/ethnicity, study design, inclusion criteria, and main findings. FINDINGS: There is insufficient evidence to confirm that menopause is associated with urinary symptoms. The effect of HT on urinary symptoms depends on type. Systemic HT may cause urinary incontinence or worsen existing urinary symptoms. Vaginal estrogen improves dysuria, frequency, urge and stress incontinence, and recurrent UTI in menopausal women. CONCLUSIONS AND RELEVANCE: Vaginal estrogen improves urinary symptoms and decreases the risk of recurrent UTI in postmenopausal women.