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Short term Metabolic Effects of Two Novel Oral Androgens, Dimethandrolone Undecanoate and 11β-MNTDC Supplemental File

Supplemental File

11B-MNTDC 28 Day Study Supplemental File

We performed a 28-day daily dosing pharmacokinetic and pharmacodynamic study of a novel oral androgen dimethandrolone undecanoate, DMAU, in healthy men. DMAU showed marked suppression of serum gonadotropins and testosterone in men, while being well-tolerated. There were no safety concerns in this 28-day study. Further studies are ongoing to assess the ability of DMAU to suppress spermatogenesis.

We performed a 28-day daily dosing pharmacokinetic and pharmacodynamic study of a novel oral androgen dimethandrolone undecanoate, DMAU, in healthy men. DMAU showed marked suppression of serum gonadotropins and testosterone in men, while being well-tolerated. There were no safety concerns in this 28-day study. Further studies are ongoing to assess the ability of DMAU to suppress spermatogenesis.

Safety and Pharmacokinetics of Oral 11βMNTDC - supplemental data

Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study--XO, XX, XY and XXY--to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic" and "cerebelo-pontine-thalamo-cortical"), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA.

We describe the use of serum cortisol and ACTH levels on postoperative d 1 and 2 as remission predictors after transsphenoidal surgery for Cushing's disease (CD).Morning cortisol and ACTH levels were drawn daily after surgery; glucocorticoids were withheld until evidence of hypocortisolemia. Early remission was defined retrospectively as a subnormal morning cortisol level [or =140 nmol/liter (or =5 microg/dl)] on postoperative d 1 or 2 and sustained remission as subsequent eucortisolemia.Of 40 consecutive adults with CD (mean age 39 yr), 80% achieved early remission. Of 39 patients with a minimum follow-up of 14 months (mean 33 months), 31 (79.5%) achieved sustained remission at a mean follow-up of 32 months, including 30 of 31 (97%) with early remission and one of eight (12%) without early remission (P0.0001). Sustained remission was achieved in 26 of 28 (93%) patients having their first operation, compared with five of 11 (45%) with a prior unsuccessful operation (P0.001). For the 32 patients in early remission vs. the eight in nonremission, mean nadir cortisol levels were 57.6 +/- 33.0 (2.05 +/- 1.2 microg/dl) vs. 631.1 +/- 352.2 nmol/liter (22.9 +/- 12.8 microg/dl) (P0.0001), and nadir ACTH levels were 11.9 +/- 6.5 vs. 64.1 +/- 54.6 ng/liter (P0.001). Of 31 patients with sustained remission, 100% had subnormal morning cortisol levels, whereas 31% had subnormal ACTH levels (P0.0001).Serum morning cortisol levels on postoperative d 1 and 2 without glucocorticoid replacement provide a safe, simple, and reliable measure of early remission for CD and are predictive of sustained remission. This method allows for consideration of a repeat operation during the same hospitalization in patients with persistent hypercortisolemia.