M. Tagliabue

PAI-1 reduction after treatment with glutathione in NIDDM

Summary The increase of the plasminogen activator inhibitor 1 (PAI-1) is considered a biological risk factor of coronary heart disease and is observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). In vitro, hyperglycaemia increases PAI-1 production by generating free radicals and the antioxidant defences reduce this phenomenon. In order to evaluate the effect of glutathione (GSH) on PAI-1, 10 patients with NIDDM underwent a treatment with GSH i.m. for 10 days. The plasma PAI-1 levels were reduced significantly after the treatment (80.1±5.2 vs 68.4±5.9 ng/ml, p

Acute goserelin administration inhibits gonadotropin and androgen secretion in post-menopausal women with ovarian hyperandrogenism

The aim of this study was to verify the effect of goserelin, a GnRH agonist, in women with post-menopausal virilization. Six patients with post-menopausal virilization and increase in 17-hydroxyprogesterone (17-OHP), total (TT) and free testosterone (FT) levels underwent single subcutaneous administration of goserelin, 3.6 mg. Serum 17-OHP, TT, FT, LH, FSH, E2, Δ4 and 3α-androstanediol glucuronide levels were measured before and 4, 8 and 18 days after goserelin administration. Goserelin administration was followed by progressive inhibition of FSH and LH, which fell to premenopausal levels on day 18, and progressive normalization of androgen parameters. The low E2 levels recorded at baseline were further reduced by goserelin administration. Four patients then underwent ovariectomy while in two patients, rejecting surgical treatment, goserelin treatment was protracted up to 6 and 12 months, respectively, with remission of hyperandrogenism. This study shows that in post-menopausal patients with virilization GnRH agonist allows to confirm the diagnosis of gonadotropin-dependent ovarian hyperandrogenism: its administration induces inhibition of gonadotropin levels, normalization of androgen parameters, and remission of virilization when the treatment is protracted in patients waiting for surgery.

Terapia dell’androgenizzazione cutanea nella donna

RiassuntoL’androgenizzazione cutanea femminile, espressa da iperseborrea, acne, ipertricosi e defluvium capitis, è determinata da un’iperstimolazione dell’apparato pilo-sebaceo da parte degli androgeni. Può essere idiopatica o sintomatica ed è efficacemente trattata con farmaci ad attività antiandrogena. In questa rassegna vengono illustrate le molecole dotate di attività antiandrogena, il loro meccanismo d’azione, gli effetti collaterali e gli schemi terapeutici più maneggevoli ed efficaci utilizzabili nella pratica clinica.

Treating varicocele in 2018: current knowledge and treatment options

PurposeVaricocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects.MethodsWe conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: “varicocele”, “varicocelectomy”, “sclerotherapy”, “male infertility”, “subfertility”, and “semen abnormalities”.ResultsData from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach.ConclusionsVaricocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

A case of deep vein thrombosis in a young male treated with tamoxifen for idiopathic infertility.

blood cells 4 800 000 mm−3 (n.v. 4 500 000–6 000 000), hemoglobin 14.4 g dl−1 (n.v. 13.5–17.5), hematocrit 42.5% (n.v. 41–50), fibrinogen 362 mg dl−1 (n.v. 200–400), prothrombin time 15 s (n.v. 16–20), international normalized ratio 1.07 (n.v. 0.85–1.25), and activated partial thromboplastin time 1.13 s (n.v. 0.82–1.24). Suspecting DVT, a lower limbs Doppler ultrasonography of the deep venous system was performed, showing a partial obstruction with internal thrombus from the left popliteal vein to the left external iliac vein. After diagnosis of DVT, a thrombophilia screening was performed, revealing an increased activity of clotting factor VIII (Table 1). Testosterone levels were not measured in the absence of signs and symptoms suggestive of testosterone deficiency.5 Anticoagulant treatment with low-molecular-weight heparin (enoxaparin) was initiated along with warfarin for 5 days. After the therapeutic range was reached (i.e. prothrombin time 2–3 by international normalized ratio), treatment was continued with warfarin alone. On discharge, D-dimer levels were reduced (6.96 μg ml−1) and Doppler ultrasonography of the deep venous iliac – femoral – popliteal system showed signs of initial revascularization and thrombus dissolution. Among different treatments proposed for idiopathic male infertility, anti-estrogens, like tamoxifen, may be taken into account. Tamoxifen seems to have a positive effect on sperm count and concentration in eugonadal patients, but it does not improve other semen parameters such as motility, morphology, and viability probably due to its effects on the first steps of spermatogenesis.6 Literature data suggest a better effect of tamoxifen in patients with low FSH levels, suggesting the need for a well-functioning hypothalamic-pituitary-gonadal axis. On the other hand, oxidative stress has well-recognized deleterious effects on sperm function. Estrogens have been shown to modulate the antioxidant system in human semen, and this provides a further rationale for antiestrogen administration in male infertility.7 Noteworthy, tamoxifen, which is widely used as adjuvant therapy for breast cancer in women, increases the risk of thromboembolic events.8 To the best of our knowledge, no known clotting abnormalities in males treated with tamoxifen for idiopathic infertility have been reported, also because it is used as an off-label treatment and rigorous safety analyses are lacking. The potential mechanism for the procoagulant effect of tamoxifen has not been fully elucidated, although a reduction in antithrombin III and protein C levels or an APC resistance phenotype have been reported.9 We conclude that immobilization due to the recent long haul trips along with the use of tamoxifen-induced a hypercoagulable state, thus increasing the risk of thrombosis in this patient. We observed Dear Editor, We present here a case of idiopathic male infertility who developed deep vein thrombosis (DVT) with the use of tamoxifen, a selective estrogen receptor modulator, probably through a hypercoagulable state. A selective estrogen receptor modulator (SERM) is a compound that can act as an estrogen agonist or antagonist, depending on the specific target tissue. At present, four SERMs are approved for clinical use: clomiphene, raloxifene, tamoxifen, and toremifene. In women, SERMs are widely used as adjuvant therapy for breast cancer. SERMs in males have been suggested as an empiric treatment for idiopathic infertility, but relatively few studies are currently available.1 Tamoxifen administration in males indirectly stimulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion by blocking estrogen receptors in the hypothalamus and pituitary gland, thus increasing the hypothalamic release of gonadotrophic releasing hormone (GnRH). The major effect of tamoxifen administration is the stimulation of Leydig cells to produce testosterone and of Sertoli cells to improve the testicular environment for spermatogenesis.2 Noteworthy, tamoxifen has also been reported to directly stimulate Leydig cells and 5α-dihydrotestosterone production in seminiferous tubules and epididymis.3 Tamoxifen increases the risk of venous thrombosis by 2to 3-fold.4 The underlying mechanisms in patients receiving tamoxifen have not been completely elucidated yet, although a decrease of several coagulation inhibitors has been reported. Tamoxifen-associated changes of the coagulation system differ substantially from estrogen-induced alterations, still it has been hypothesized that tamoxifen also induces an activated protein C (APC) resistance phenotype.4 A 36-year-old Caucasian male was admitted for severe pain at his left lower limb. The patient was alert, fully oriented, and did not have fever. His left leg was disproportionately large by inspection, with warm, reddened, and edematous skin. The patient had taken tamoxifen 20 mg daily for 3 months for idiopathic male infertility in a program of assisted reproduction. Moreover, he had a recent history of long haul car and train trips. He was normal weight (body mass index, BMI 23.5 kg m−2), eugonadal at the beginning of tamoxifen treatment (total testosterone 4.3 ng ml−1), and a nonsmoker. Blood tests performed on admission showed coagulation abnormalities, but no erythrocytosis nor thrombocytosis: D-dimer 11.12 μg ml−1 (normal values, n.v., <0.8), platelet count 177 000 μl−1 (n.v. 150 000–450 000), red A case of deep vein thrombosis in a young male treated with tamoxifen for idiopathic infertility