Male PCOS equivalent and nutritional restriction: Are we stepping forward?

Polycystic ovarian syndrome (PCOS) is an endocrine disorder characterized by alteration of menses, polycystic ovaries, clinical and or biochemical signs of hyper-androgenism in the context of metabolic abnormalities such as obesity and insulin resistance that play a fundamental role in pathogenesis of the disease as well as in development of long-term complications including cardiovascular disease (CVD) and type II diabetes mellitus (DM II). Latest evidence supports the hypothesis of a genetic component in the aetiology of PCOS that seems to be inherited through an oligo-genic mechanism and cluster in families. Recent studies identified the existence of a male PCOS correspondent syndrome in which the genes responsible for PCOS susceptibility in women may be inherited by male relatives of women with PCOS. The same hormonal, clinical and metabolic alterations of women with PCOS have been found in their male relatives suggesting a relation between the syndrome in its male equivalent. Considering clinical manifestations of male PCOS equivalent, the early onset andro-genetic alopecia (AGA) is considered a clinical marker of insulin resistance, supported by the findings of a case-control study that reported an increased prevalence of hyperinsulinemia and insulin-resistance-associated disorders such as dyslipidaemia, hypertension and obesity, in men with early onset of alopecia (<35), compared with age-matched controls. Moreover, AGA and insulin resistance show higher levels of active androgens, highlighting that low SHBG levels occur in both the diseases and that the two conditions may concur to a worsening of the disease. With regards to the existence of a male PCOS equivalent syndrome, in particular with refer to its phenotypic hallmark of early onset AGA, our hypothesis supposes a beneficial effect of diet restriction used for PCOS as therapy for male patients affected by PCOS equivalent syndrome. Several observational studies and some randomized trials reported that modest reductions of body weight decrease the risk of development of many diseases, including diabetes and cardiovascular disease and contributes to increase insulin sensitivity in PCOS women. Weight reduction may be adopted for men affected by PCOS equivalent syndrome in order to reduce both levels of circulating androgens, insulin resistance and related-complications such as CVD and DM II.

[Nebido in the treatment of hypogonadism syndrome and its complications in men].

The article presents original experience with use of undecanoate (nebido, BayerHealthcare Pharmaceuticals, Germany) in androgenic testosteron replacement therapy in males with hypogonadism. Prospective studies of nebido efficacy were made in males with vein-occlusive erectile dysfunction (n = 20), chronic pelvic pain syndrome (n = 77), metabolic syndrome (n = 170). Retrospective studies assessed efficacy of nebido monotherapy in patients with erectile dysfunction and hypogonadism (n = 34), hematological and urological safety of the drug (n = 40). Laboratory monitoring was performed in all the studies according to ISSAM recommendations. The patients were not included in contraindications to androgenic therapy. Nebido treatment significantly improved libido and erectile function, efficacy of phosphodiesterase of type 5 inhibiors used in moderate and severe erectile dysfunction. Depressive, asthenic, pain symptoms declined in males with chronic pelvic pain. Body fat reduced in metabolic syndrome with alleviation of its other components. Insignificant rise of hemoglobin level and packed cell volume was observed in some patients while a PSA level increase was clinically significant in 10% patients who had initial PSA > 2.5 ng/ml and acromegalia. Also, nebido depressed production of gonadotropins and spermatogenesis. Thus, nebido is highly effective in sexual dysfunction and other somatic disorders caused by hypogonadism. Nebido does not induce severe side effects, but clinically significant rise of PSA level requires treatment discontinuation and more careful urological examination. In view of nebido ability to suppress spermatogenesis, the drug should not be used in reproductively active men.

Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases.

Hypogonadism, erectile dysfunction (ED), visceral adiposity, insulin resistance and metabolic syndrome (MetS) often coexist in the same subjects. This cluster of abnormalities is associated with an increased risk of diabetes and cardiovascular diseases (CVD), affecting not only quality of life but also life expectancy. Longitudinal studies have also demonstrated that ED and male hypogonadism could be considered surrogate markers of incident CVD and MetS. However, how androgens signal fat depots and lessen them is still a matter of active research and whether or not low testosterone could play a pathogenetic role in CVD is still under debate. Hence, pathogenetic mechanisms linking hypogonadism with obesity and insulin resistance appear to be complex and often multi-directional. Visceral obesity can probably be considered a relevant cause of hypogonadism but at the same time, hypogonadism could be a cause of obesity and insulin resistance, consequently establishing a vicious cycle. To provide a critical analysis of these issues, a comprehensive literary search was carried out to discuss the relationship between insulin resistance ED, visceral adiposity, MetS and hypogonadism focusing on their possible involvement in the development of CVD.

Cancer of the urinary bladder neovagina in a patient with Morris' syndrome.

BACKGROUND: Vaginal agenesis is a rare condition, therefore the incidence of a malignant transformation in the neovagina is extremely low. CASE REPORT: We report on a 42-year-old patient with Morris' syndrome and urinary bladder neovagina with a history of prolonged infections of the urinary bladder and intertrigo of the perineal region. The biopsy revealed a squamous cell carcinoma arising from the neovagina. The patient underwent combined radio- and chemotherapy and was disqualified from surgical treatment because of the advanced stage of the disease. CONCLUSIONS: Because of the high risk of malignant transformations regular follow-ups are necessary in patients with neovagina creation, including gynecological examination, cytological screening, and biopsy if necessary. In addition, urinary bladder does not seem to be a good material for a functional vagina.

Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization).

Graham Little-Piccardi-Lassueur syndrome is characterized by the presence of cicatricial alopecia on the scalp, keratosis pilaris in the skin of trunk and extremities, and non-cicatricial hair loss in pubis and axillae. A frequent form of male pseudohermaphroditism is complete androgen insensitivity syndrome (CAIS), also known as testicular feminization syndrome. It refers to genetic males with XY karyotype who, owing to a lack of sensitivity in the peripheral androgenic receptors, develop a female phenotype. Axillary and pubic hair is typically scarce or absent. To our knowledge, this is the first case describing the association of the two processes. The presence of both processes in the same patient furthers our understanding of Graham Little-Piccardi-Lassueur syndrome as it rejects the influence of androgens in the alopecias accompanying this syndrome. The coincidence of non-cicatricial alopecia in axillary and pubic hair in both processes is also remarkable.

Tumors of the testis in intersex syndromes.

Patients with intersex syndrome are rare in the general population. In these patients, cryptorchid gonads that have an Y chromosome or Y chromosomal material are at risk for development of germinal and non-germinal neoplasm and non-neoplastic masses. Diagnosis of individual patients should be accurate for optimal care and risk assessment.

Development of a hypoplastic uterus in a patient with testicular feminization syndrome 21 years after gonadectomy.

We describe a case of hypoplastic uterus, identified by transrectal ultrasonography and magnetic resonance imaging, which developed 21 years after gonadectomy for testicular feminization syndrome. Its likely origin was Müllerian-fusion remnant resulting from a deficiency in functional Müllerian inhibiting substance (MIS) and/or desensitization of the Müllerian tract to MIS, caused by diethylstilbestrol administration to the patient's mother during the sensitive period of the 6th and 9th gestational weeks of her pregnancy. This Müllerian-fusion remnant remained latent, due to insufficient estrogen stimulation both endogenously (until gonadectomy) and exogenously during hormone replacement therapy. Initial growth was possible induced in response to high doses of estrogen that the patient received over the last 3 years for the treatment of osteoporosis.

Yolk sac tumor in a case of testicular feminization syndrome.

A 17 month old who had been diagnosed as having testicular feminization syndrome (noted during inguinal herniorrhaphy) was operated on because of an abdominal mass that had a high serum level of alpha-fetoprotein. Histologically, the lesion was a yolk sac tumor. The alpha-fetoprotein level normalized within 2 months of the surgery, through the administration of adjunctive chemotherapy containing cisplatinum. The patient is disease-free 4 years postoperatively. When performing inguinal herniorrhaphy in a girl, the surgeon should be prepared to deal with testicular feminization syndrome. If gonadal neoplasm is deniable at the time of diagnosis, careful follow-up examinations are needed until completion of the development of secondary sex characteristics.

[Association of Morris' syndrome with squamous cell carcinoma of the vulva]. / Association du syndrome de Morris avec le carcinome à cellules squameuses de la vulve.

We described a case of squamous cell carcinoma of the vulva in a patient with Morris' syndrome. In these patients, there is an increased risk of gonadal neoplasms. On the contrary, neoplasms originating from the vulvo-vaginal tract are very rare. Neoplasms arising from the neovagina have been reported. Therefore, a continued periodic surveillance of the external genitalia and the vagina is indicated.

Seminoma in pubertal patient with androgen insensitivity syndrome.

The case of a 14-year-old girl with complete androgen insensitivity syndrome and metastatic seminoma is reported. She was treated by bilateral adnexectomy, removal of paraaortic lymph nodes, postoperative radiation, and estrogen replacement therapy. She represents the fourth case of gonadal malignancy to be reported in a teenage patient with androgen insensitivity syndrome.

[A case of Kennedy-Alter-Sung syndrome associated with external ophthalmoplegia--therapeutic efficacy of fluoxymesterone].

We reported a case with Kennedy-Alter-Sung syndrome (KAS) associated with bilateral external ophthalmoplegia. The patient had movement disturbance of bilateral infra-oblique muscles. The doll's eye phenomenon was not noted. It was suggested that the external ophthalmoplegia was due to the involvement of the oculomotor nucleus that innervated infra-oblique muscle. The serum levels of testosterone and gonadotropin were high, suggesting that the feminization of KAS patients was caused by androgen insensitivity. The feminization of KAS patients is similar to the incomplete form of testicular feminization syndrome except that they do not have feminization of genitals. Therefore, we proposed that abnormalities of androgen receptors might play a role in the pathogenesis of KAS. Fluoxymesterone therapy significantly improved the muscle weakness of the extremities of the patient, even though the therapeutic efficacy was shown temporarily. The therapeutic efficacy of fluoxymesterone for muscle weakness supports our hypothesis.

The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism.

The evidence that supports the hypothesis that insulin and LH both regulate ovarian androgen production was presented. The most dramatic clinical example of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. Our hypothesis is that, in the HAIR-AN syndrome, the severe insulin resistance causes a compensatory hyperinsulinemia, which stimulates ovarian androgen production if adequate LH is present. The acanthosis nigricans is an epiphenomenon of the syndrome. Acanthosis nigricans is a dermatologic manifestation of severe insulin resistance. In vitro evidence suggests that insulin and IGF-I stimulate androgen production in incubations of human stroma and theca. The stromatropic effects of insulin may sensitize the stroma to the stimulatory effects of LH. In some hyperandrogenic-insulin-resistant women, a glucose load appears to produce an acute rise in circulating androgens. The magnitude of the rise in circulating androgens is proportional to the magnitude of the insulin response to the glucose load. These data suggest that hyperinsulinemia may play a central role in the development of ovarian hyperandrogenism.