Osteoporosis and male age-related hypogonadism: role of sex steroids on bone (patho)physiology.

Male age-related bone loss is caused, at least in part, by hypogonadism that occurs with advancing age. The study of the effects of sex steroids on bone physiology in men has recently highlighted the central role of estrogens on bone pathophysiology. This review focuses on particular aspects of bone physiology and pathophysiology in aging men, noting both the similarities to and the differences from female counterparts. In particular, the role of sex steroids on bone sexual dimorphism in health and disease has been analyzed.

Aromatase is differentially expressed in peripheral blood leukocytes from children, and adult female and male subjects.

OBJECTIVE: Aromatase, the key enzyme involved in estrogen synthesis, is expressed in a variety of cells and tissues including human peripheral blood leukocytes (PBLs). The present study was designed to evaluate PBL aromatase gene expression in male and female subjects of different age groups. In addition, differences in gene expression during the follicular and luteal phase of the menstrual cycle in women, and before and after testosterone administration in men, were estimated. DESIGN: Aromatase mRNA and protein were measured in PBLs obtained from young (n = 10) and postmenopausal women (n = 10), men (n = 15), and prepubertal children (n = 10). Aromatase mRNA and protein were also measured during the follicular and luteal phases of the menstrual cycle in women, and before and after the intramuscular administration of 250 mg testosterone enanthate in men. METHODS AND RESULTS: Aromatase mRNA measured by real-time PCR in PBLs from women during the follicular phase was significantly higher than during the luteal phase of the menstrual cycle (P < 0.05). In men, PBL aromatase mRNA values increased significantly following testosterone administration (P < 0.05). PBL mRNA aromatase levels in women during the follicular phase and men after testosterone administration were significantly higher (one-way ANOVA; P < 0.05) than in any other group. Children, postmenopausal women, and women during the luteal phase showed the lowest aromatase mRNA expression. The results of the immunoblot analysis confirmed the data obtained by real-time PCR. A positive correlation between PBL aromatase mRNA values and plasma estradiol and estrone levels during the follicular phase of the menstrual cycle was observed in the group of adult women. No other correlations were found. CONCLUSIONS: The aromatase gene is differentially expressed in PBLs from women, men, and prepubertal children, indicating a sexual dimorphism in the enzyme expression and an important role of sex steroids in the modulation of aromatase gene expression.

The effects of long-term raloxifene and estradiol treatments on bone in a patient with congenital aromatase deficiency.

INTRODUCTION: In adult aromatase-deficient men, estrogen treatment has always resulted in a rapid skeletal maturation with epiphyseal closure and improved BMD. Raloxifene is a SERM with proven estrogen agonist action on bone that leads to an improvement in BMD and a reduction in bone turnover. The present study reports the effects of raloxifene and transdermal estradiol treatment, respectively, on epiphyseal closure and BMD in an aromatase-deficient man, over a 24-month follow-up, with the aim of obtaining further insight into the role of estrogens in the male skeletal homeostasis. MATERIALS AND METHODS: A 25-year-old Caucasian man with aromatase deficiency, a bone age of 15.3 years, unfused epiphyses and an impaired BMD was initially administered raloxifene (60 mg/day per os) for 12 months, while transdermal estradiol (25 microg twice weekly) was administered for the subsequent 12 months. During the follow-up, the effects of the two treatments on epiphyseal closure, BMD and bone turnover markers were investigated. An iliac crest bone biopsy was performed only before and after the raloxifene treatment, but it was not repeated after transdermal estradiol treatment. RESULTS: No changes in bone age were observed after raloxifene therapy, whereas a complete epiphyseal closure was achieved with transdermal estradiol treatment. Compared with baseline values, raloxifene treatment led to improved BMD both at the ultradistal forearm and 33% radius; the transdermal estradiol treatment resulted in a further slight increase in BMD at the 33% radius, but not at the ultradistal forearm. The baseline bone biopsy showed elevated bone remodelling in trabecular bone, while the second biopsy following raloxifene treatment revealed a decrease in remodelling. DISCUSSION: This study shows that the management of aromatase deficiency in the male cannot consider raloxifene as a first choice treatment, but should be still based on estrogen replacement treatment since in this patient the completion of bone maturation has only been obtained once estradiol substitution was performed. The present case also demonstrates that raloxifene is able to improve BMD in aromatase-deficient men.

Differentiated thyroid carcinoma (DTC) in a young woman with Peutz-Jeghers syndrome: are these two conditions associated?

AIMS: Peutz-Jeghers Syndrome (PJS) is a rare dominantly inherited disease characterized by hamartomatous small bowel polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer. Differentiated thyroid cancers (DTCs) present mainly as sporadic, but they may have also a familial component. We present a case of PJS in a caucasian 25 years-old woman, who developed a DTC. METHODS: The patient had a palpable nodule in the right side of the thyroid region and an endocrinological evaluation, including hormonal assays, neck ultrasound (US) and fine needle aspiration (FNAB) of the nodule was performed. RESULTS: US confirmed a single nodular lesion in the right thyroid lobe (14 mm). Cytological analysis at FNAB revealed a pattern compatible with papillary thyroid carcinoma. The histological analysis after total thyroidectomy confirmed the diagnosis of a Hurtle cell variant of papillary thyroid carcinoma, with follicular architecture. CONCLUSION: Even though rare, the association between PJS and DTC can be possible. In clinical practice it must be borne in mind that the wide spectrum of possible cancer diseases occurring in PJS could also include DTC, that the latter can occur earlier in life in PJS population and with a more aggressive histological pattern. Furthermore, in patients with PJS, US of the thyroid should be performed whenever thyroid disease is suspected at physical examination or based on patient's medical history. Due to lack of established data allowing for a real esteem of the association between PJS and DTC, US of the thyroid, should not be recommended as a routine screening for all subjects with PJS.

Hypopituitarism and HIV-infection: a new comorbidity in the HAART era?

Several comorbidities are associated with the HIV infection and may involve also the endocrine-metabolic system. Consistently, the recent development of the therapeutic regimen highly active antiretroviral therapy (HAART) ruled out a significant improvement both in the prognosis and life expectancy of HIV-infected patients, but disclosed also new serious drug-related toxicity. Of these, the lipodystrophy syndrome is the most frequent, occurring in up to 83% of HIV-infected patients under HAART. The HIV-related lipodystrophy is associated with alterations in GH dynamics, affecting both basal and stimulated GH secretion. This GHIGF- I secretive pattern resembles that of severe GH deficiency in adulthood due to pituitary diseases, but without leading to IGF-I serum levels below the normal range. The impairment of pituitary GH secretion has been ascribed to the hormonal and metabolic inhibitory effect due to adipose tissue redistribution in HIV-infected males, since in these patients pituitary GH secretion appeared to be inversely related to visceral adipose tissue accumulation and waist to-hip-ratio. However, whether these patients suffer from a true GH deficiency due to an intrinsic pituitary failure or display only a functional reduction of GH secretion due to visceral adiposity remains still a matter of debate, especially in HIV-infected females.

Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men.

AIMS: The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2). METHODS: The effects of transdermal oestradiol (tE(2)) treatment at different dosages on insulin sensitivity were studied before tE(2) treatment (phase 1), and after 6 months (phase 2) and 12 months of tE(2) treatment (phase 3) by means of homeostasis model assessment-insulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), insulin tolerance test (ITT), and oral glucose tolerance test (OGTT). The latter was performed only in subject 1, as subject 2 suffered from Type 2 diabetes. RESULTS: The restoration of normal serum oestradiol led to improved insulin sensitivity, as shown by changes in HOMA-IR and QUICKI. The ITT provided evidence of improved insulin sensitivity during tE(2) treatment. Insulin secretion after OGTT was reduced during tE(2) treatment in subject 1. After 12 months of tE(2) treatment, insulin sensitivity was improved compared with in phases 1 and 2. CONCLUSIONS: The study suggests a direct involvement of oestrogens in insulin sensitivity, and supports a possible role of oestradiol : testosterone ratio, which may be as influencial as the separate actions of each sex steroid on glucose homeostasis.

Bone loss, sex steroids and male age related hypogonadism.

Male age-related bone loss is caused at least in part from hypogonadism that occurs with advancing age. Recently, the study of sex steroids on bone physiology in men has highlighted the central role of estrogens on bone pathophysiology. This review focuses on the relative role of sex steroids on bone loss in aging men.

Sex steroids and sexual desire mechanism.

Sexual behavior is mainly controlled by cognitive functions in men, though hormones, particularly sex steroids, may modulate some aspects of male sexuality. This review focuses on the role of both estrogens and androgens on male sexual desire, starting from both animal and human studies. Estrogens could play a role in human male sexual activity, similarly to what happens in animals, but even though physiological levels of estrogens could be probably required for a completely normal male sexual behavior, testosterone remains the major determinant of human male sexual behavior.