Sexual dimorphism in the assessment of mineral apposition rate during osteoporosis

The objective of this study was to evaluate the daily maxillary and tibial bone mineral apposition rate of ovariectomized rats and orchiectomized rats through confocal laser microscopy. Twenty-four animals were divided into 4 groups (SHAMF, OVX, SHAMM and ORQ). Six rats were distributed to the SHAMF group (submitted to fictitious surgery); six rats to the OVX group (submitted to bilateral ovariectomy); six rats to the SHAMM group (submitted to fictitious surgery) and six rats to the ORQ group (submitted to bilateral orchiectomy). On the 60th day after the surgical procedures the animals received 20 mg/kg of calcein and after 24 days 20 mg/kg of alizarin red was administered. The euthanasia was performed 18 days after the last fluorochrome administration. The histological slides obtained were submitted to confocal microscopy analysis and then dynamic histomorphometry was performed to obtain the daily mineral apposition rate (MAR). In the tibias, the values of MAR were higher for the SHAMF group (P<0.05) (mean: 37.1μm² / day) compared to the ORQ group (mean: 7.16 μm²). In the jaws, the values were higher for the SHAMF group (P<0.05) (mean: 5.175μm² / day) compared to the SHAMM group (mean: 1.84 μm²), OVX (mean: 3.027 μm²) and ORQ group (mean: 1.56 μm²). It can be concluded that the female gender, regarding the characteristics of the maxillary and tibial bones, presented a daily mineral bone apposition rate higher than the male gender, mainly in the maxillary bone, presenting a statistically significant difference between all groups studied.

Bilateral Orchiectomy With or Without Flutamide for Metastatic Prostate Cancer

This chapter summarizes the findings of a landmark randomized trial comparing total androgen deprivation in the form of bilateral orchiectomy plus the antiandrogen flutamide to bilateral orchiectomy alone. The study found no survival benefit but did find increased side effects from the addition of an antiandrogen.

Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer

Since 1944, when Huggins and Hodges demonstrated the effectiveness of bilateral orchiectomy for metastatic prostate cancer (PCa), androgen deprivation therapy (ADT) has been the first-line treatment for men with advanced PCa. The proportion of PCa cases that are metastatic at diagnosis ranges globally, from 5%–20% in countries with widespread screening practices to upward of 30%–60% where screening is minimal. In the United States alone, there will be an estimated 191,000 new cases of PCa diagnosed in the year 2020, of which approximately 20% will be metastatic. 1 Ongoing controversy around prostate-specific antigen (PSA) screening practices, increased access to novel imaging modalities, and a globally aging population will drive increased rates of metastatic castration-sensitive prostate cancer (mCSPC). 2 , 3 At the same time, advances in upfront hormonal or chemohormonal therapy have driven a dramatic shift in treatment paradigms. In this article, we review recent advances in treatment choices for men with newly diagnosed mCSPC and the impact of upfront treatment on subsequent disease biology. Options include treatment with chemohormonal therapy, androgen receptor (AR)–directed therapy in addition to ADT, or, less commonly, ADT alone. Treatment choice must include consideration of clinical and disease characteristics, as well as patient preferences and limitations of geography and financial concerns.

Testosterone modulates renal ammonia metabolism

There are substantial sex differences in renal structure and ammonia metabolism that correlate with differences in expression of proteins involved in ammonia generation and transport. This study determined the role of testis-derived testosterone in these differences. We studied 4-mo-old male C57BL/6 mice 4 and 8 wk after either bilateral orchiectomy (ORCH) or sham-operated control surgery and determined the effect of testosterone replacement to reverse the effects of ORCH. Finally, we determined the cellular expression of androgen receptor (AR), testosterone’s canonical target receptor. ORCH decreased kidney and proximal tubule size, and testosterone replacement reversed this effect. ORCH increased ammonia excretion in a testosterone-dependent fashion; this occurred despite similar food intake, which is the primary component of endogenous acid production. ORCH increased expression of both phospho enolpyruvate, a major ammonia-generating protein, and Na+-K+-2Cl− cotransporter, which mediates thick ascending limb ammonia reabsorption; these changes were reversed with testosterone replacement. Orchiectomy also decreased expression of Na+/H+ exchanger isoform 3, which mediates proximal tubule ammonia secretion, in a testosterone-dependent pattern. Finally, ARs are expressed throughout the proximal tubule in both the male and female kidney. Testosterone, possibly acting through ARs, has dramatic effects on kidney and proximal tubule size and decreases ammonia excretion through its effects on several key proteins involved in ammonia metabolism.

Pituitary as a Source of HCG: Residual Levels After Bilateral Testicular Tumor Removal

Context. Challenging clinical scenario in which elevated β-human chorionic gonadotropin (HCG, subsequently termed HCG) levels suggested occult tumor metastases after removal of bilateral testicular cancers and metastases from them and as well as after chemotherapy. Case Report. A 22-year-old male, post excision of bilateral testicular tumors, who had no imaging or clinical evidence of residual tumor but an elevated HCG raising the question of the presence and location of occult tumor metastases. Clinical Questions. Does luteinizing hormone (LH) cross-react with HCG in current assays? What levels of testosterone and estradiol are necessary to suppress LH and follicle-stimulating hormone (FSH) in a male patient with bilateral orchiectomy, and therefore lacking inhibin? Does the pituitary secrete HCG and under what circumstances? Assessment. Current HCG assays no longer cross-react with LH as did prior assays, but the presence of heterophile antibodies and other factors such as biotin can still cause false positive HCG levels. In the chronic post-orchiectomy state, the pituitary is relatively resistant to LH and FSH suppression by testosterone. The pituitary secretes HCG in very small amounts unless interruption of negative feedback results in high LH and FSH whereupon HCG levels become elevated. Clinical Conclusion. A GnRH antagonist suppressed both LH and HCG in this patient indicating that the elevated HCG was secreted by the pituitary and not by occult tumor metastases. Further credence for this conclusion resulted from the lack of a progressive increase in HCG levels over a 4-year period of follow-up and from no evidence of metastatic tumors on serial imaging.