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Background: 3,3'-diindolylmethane (DIM) is a phytonutrient derived from cruciferous vegetables that is an often-used supplement in the complementary and alternative medicine space. The most common goal for providers when recommending DIM to their patients is to alter estrogen metabolism, yet research into DIM's effect on the estrogen profile is lacking in the published literature. The objective of this study was to comprehensively evaluate DIM's effect on the urinary estrogen profile., Methods: In this retrospective cohort study, we analyzed data from a clinical laboratory, including urinary estrogen and estrogen metabolite concentrations. Analyte concentrations were determined from dried urine samples using a gas chromatography-tandem mass spectrometry assay. Individuals were separated into two groups, either reporting taking DIM (N = 909) or reporting not taking DIM (N = 18,385). Comparisons between individuals in these two groups were made using the Wilcoxon rank sum test. Additionally, we were also able to explore a subset of women who had laboratory results in the database before and after initiating DIM treatment (N = 53). In this subset, differences were assessed with Wilcoxon signed rank tests., Results: In the larger group that was separated into women reporting either DIM use or no use, significant differences were observed in the concentrations of almost every urinary estrogen and estrogen metabolite (with the only exception being 2-methoxyestrone) in the urinary estrogen profiles of those taking DIM compared to those not taking DIM (all P values < 0.001). In the smaller subset of individuals with results before and after initiating DIM use, differences were only seen in 4 of the urinary estrogens and estrogen metabolites (P < 0.001 for estrone, estradiol, estriol, and 16-hydroxyestrone). Differences in total estrogens were significant in both the larger group and the smaller subset (both with P < 0.001). Additionally, observed differences in the ratios of metabolites followed a similar trend with more significant differences observed in the larger group. Notably, the 2-hydroxyestrone:16-hydroxyestrone ratio increased significantly in both the larger group and the smaller subset with results before and after DIM use., Conclusions: The results of this study provide the most comprehensive evaluation to date of DIM's effect on the urinary estrogen profile. Additionally, the results demonstrate that the dried urine collection and accompanying assay used capture changes that are similar in direction, but not necessarily magnitude, to previous reports in the literature. Considered together, these two things highlight the clinical validity and utility of this approach to the evaluation of DIM supplementation and suggest the need for additional studies using this approach to fully understand the potential clinical utility of DIM., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the National University of Natural Medicine Institutional Review Board, and since all data analyzed in this data mining study were deidentified, the institutional review board determined that written informed consent could be waived. Consent for publication: Not applicable. Competing interests: M.N. is the founder and CEO of Precision Analytical, Inc. J.S. is an employee of Precision Analytical, Inc., (© 2024. The Author(s).)

Background: To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC)., Methods: Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr) and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr), and male (n = 16, age: 41.88 ± 8.48 yr) patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr), the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations., Results: Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16α-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17β-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16α-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P < 0.001). In particular, the metabolic ratio of 2-hydroxyestrone to 2-hydroxy-17β-estradiol, which could reveal the enzyme activity of 17β-hydroxysteroid dehydrogenase, showed gender differences in PTC patients (P < 1 × 10-7)., Conclusions: These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions.

The aim of this one-year prospective study was to determine whether longterm thyroxine treatment is a risk factor for elevated bone turnover, loss of bone mass and subsequent development of osteoporosis. Premenopausal women (N = 19), and men (N = 9) suffering from differentiated thyroid gland carcinoma in the mean age of 39.0 +/- 8.0 years and 41.8 +/- 10.0 years were investigated. All of them had undergone a total thyroidectomy and subsequent thyroxine therapy. The duration of the TSH-suppressive therapy prior to the the beginning of our study was 9.4 +/- 6.4 years in the female and 8.1 +/- 6.0 years in the male group. The prospective observation was performed by dual X-ray absorptiometry (DXA) at the spine and the femoral neck and by single-photon absorptiometry (SPA) at the distal radius. Laboratory testings included thyroid hormones T3, T4 and TSH, serum calcium, phosphate and PTH, and urinary calcium and phosphate from spontaneous and 24-hour urine samples. Markers of bone formation (osteocalcin, alkaline phosphatase and PICP) and resorption (Ca/Cr and ICTP) were determined. Statistically significant loss of bone mass was observed only on the distal radius in males (p<0.05). At the lumbar spine and femoral neck, only a minor bone loss was registered in a small number of patients. Almost 50 % of the females showed values above the reference range. In more than 30 % of the females, and smaller number of male patients, ICTP values ranged above the reference range, corresponding to elevated bone turnover. These two variables exhibited a slight correlation with bone density at the measured skeletal areas, mostly considering the male group. The results are a proof that accelerated bone turnover and subsequent bone loss occurs during TSH-suppressive thyroxine therapy. In future prospective studies a prolonged time of observation will be necessary, as well as to increase the number of studied patients, in order to better assess the relative risk of osteoporosis in patients undergoing TSH-suppressive treatment more precisely.