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Context: Guidelines for use of injectable estradiol esters (valerate [EV] and cypionate [EC]) among transgender and gender diverse (TGD) individuals designated male at birth vary considerably, with many providers noting supraphysiologic serum estradiol concentrations based on current dosing recommendations., Objectives: 1. Determine dose of injectable estradiol (subcutaneous [SC] and intramuscular [IM]) needed to reach guideline-recommended estradiol concentrations for TGD adults using EC/EV. 2. Describe relationship between estradiol concentration relative to timing/dose of last estradiol injection and other covariates. 3. Determine dosing differences between IM/SC EV/EC., Methods: Cross-sectional retrospective study across six United States medical centers including TGD adults on same-dose injectable estradiol for >75 days, with confirmed timing of estradiol concentration relative to last injection, from 1/1/2019---12/31/2023. Descriptive statistics were used to describe patient characteristics and weighted linear mixed models to evaluate relationship between various covariates and estradiol concentration., Results: Data from 562 patients were included. Among those injecting every seven days who reached the guideline-recommended estradiol concentration (n=131, 27.5%), the median estradiol dose was 4.0 mg (interquartile range 3.0---5.0 mg). Among all patients, the majority reached supraphysiologic estradiol concentrations (>200 pg/mL [>734 pmol/L]) while dose and timing in the injection cycle were significant covariates for the estradiol concentration. There were no significant dosing differences between IM/SC EV/EC., Conclusion: Injectable estradiol esters effectively reach guideline-recommended estradiol concentrations but at lower doses than previously recommended. Estradiol concentrations are best interpreted relative to timing of last injection. Route of administration and type of ester do not significantly impact estradiol concentrations., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objective: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route., Methods: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available., Results: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle., Conclusions: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. All rights reserved.)

The clinical need for methods to repair and regenerate large cartilage and bone lesions persists. One way to make new headway is to study skeletal regeneration when it occurs naturally. Cartilage repair is typically slow and incomplete. However, an exception to this observation can be found in the costal cartilages, where complete repair has been reported in humans but the cellular and molecular mechanisms have not yet been characterized. In this study, we establish a novel animal model for cartilage repair using the mouse rib costal cartilage. We then use this model to test the hypothesis that the perichondrium, the dense connective tissue that surrounds the cartilage, is a tissue essential for repair. Our results show that full replacement of the resected cartilage occurs quickly (within 1 to 2 months) and properly differentiates but that repair occurs only in the presence of the perichondrium. We then provide evidence that the rib perichondrium contains a special niche that houses chondrogenic progenitors that possess qualities particularly suited for mediating repair. Label-retaining cells can be found within the perichondrium that can give rise to new chondrocytes. Furthermore, the perichondrium proliferates and thickens during the healing period and when ectopically placed can generate new cartilage. In conclusion, we have successfully established a model for hyaline cartilage repair in the mouse rib, which should be useful for gaining a more detailed understanding of cartilage regeneration and ultimately for developing methods to improve cartilage and bone repair in other parts of the skeleton., (© 2014 American Society for Bone and Mineral Research.)

Background: Estrogen withdrawal has been described as a trigger for migraine headache, and some studies suggest that estrogen and progestin may exacerbate migraine. No population-based studies have examined the association between hormone therapy (HT) and migraine among postmenopausal women., Methods: To examine the association between HT and migraine headache in postmenopausal women, we used self-report of HT use, HT characteristics, and migraine headache within the past year among 17,107 postmenopausal female health professionals enrolled in the Women's Health Study., Results: Analyses were restricted to the 17,107 of 21,788 postmenopausal women who were postmenopausal at baseline and who were never (38.5%) or current (61.5%) users of HT. Of these, 1,909 (11.2%) experienced migraine headache within the last year. Women with migraine headache were significantly younger, had a younger age at menopause, were more likely to have had a surgical menopause, and were more likely to be current users of HT. After adjusting for age, race, smoking, alcohol use, ever use of oral contraception, age at menopause, and menopause type, the odds ratio (OR) for migraine headache was 1.42 (95% CI 1.24-1.62) for women who were current users of HT compared with never users. ORs were similar for users of estrogen alone (OR 1.39, 95% CI 1.14-1.69) and users of both estrogen and progestin (OR 1.41, 95% CI 1.22-1.63)., Conclusions: In this cross-sectional study, current HT use was associated with higher rates of migraine headache than nonuse. Clinical trials are needed to determine if HT increases the incidence of migraine in postmenopausal women.

Context: The results of reviews may be biased by delays in publication and failure to publish nonsignificant results., Objective: To determine the extent of unpublished results on the health effects of passive smoking and whether passive smoking studies with statistically nonsignificant results would have longer time to publication than those with statistically significant results., Design: Semistructured telephone interviews of principal investigators of published or unpublished studies funded between 1981 and 1995, identified by information obtained from 76 (85%) of 89 organizations contacted that potentially funded research on passive smoking., Participants: Seventy-eight investigators were eligible and could be located; 65 (83%) responded. They had conducted 61 studies of the health effects of passive smoke in humans or animals between 1981 and 1995 that met the criteria for the analysis of time to publication., Main Outcome Measure: Time to publication for published studies and statistical significance of results of published and unpublished studies., Results: Fourteen of the 61 studies were unpublished. Median time to publication was 5 years (95% confidence interval [CI], 4-7 years) for statistically nonsignificant studies and 3 years (95% CI, 3-5 years) for statistically significant studies (P=.004). Statistically significant results (P=.004), experimental study design (P=.01), study size less than or equal to 500 (P=.01), and animals as subjects (P=.03) were predictive of time to publication. When the studies with human participants were analyzed separately, only statistically significant data were predictive of publication (P=.007). Multivariate analysis of all studies indicated that statistical significance (P=.001) and study design (P=.01) were the only independent predictors of time to publication, while for the human studies only statistical significance was predictive of publication (P=.007)., Conclusion: There is a publication delay for passive smoking studies with nonsignificant results compared with those with significant results.