Elevated level of inhibin-α subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

The biological function of inhibin-α subunit (INHα) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHα in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHα. We conducted a cross-sectional study to determine a link between INHα expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHα in advanced cancer. Elevated expression of INHα in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INHα in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHα-positive LNCaP demonstrated reduced tumour growth whereas INHα-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHα associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHα expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa

CONGENITAL ABSENCE OF THE VAGINA - RESULTS OF CONSERVATIVE TREATMENT

Objective: To assess the efficacy of a combination of Frank's mold therapy with intercourse as a treatment for congenital vaginal aplasia. Study design: From 1973-1993, thirty-three patients with congenital aplasia of vagina and uterus were seen by one gynecologist. Patients with a partner were instructed how to create a functional vagina by a modified form of coitus ('interfemoral intercourse'). Mold therapy (using modified molds) was used as a primary treatment when patients had no partner (n = 9) or added to the treatment of nine patients in whom interfemoral intercourse alone had failed. In case of failure of conservative treatment, the surgical creation of a neovagina (McIndoe procedure) was offered. Results: Conservative therapy in patients with a stable sexual relationship (n = 24) gave significantly better (p = 0.0104) results than when patients were single. In the former, a vaginal depth of >8 cm was reached within six months at most with intercourse alone and four months if combined with mold therapy. With molds alone, 3 out of 9 obtained a satisfactory vagina. Treatment failures occurred (with one exception) only in patients who had no or unstable sexual relationships. Conclusion: Intercourse as a treatment of vaginal atresia can be very successful, especially if practised together with modified mold therapy. A stable sexual relationship - implying a healthy self-concept - appears to be an important determinant of treatment outcome

CLINICAL HISTORY AND OUTCOME OF 59 PATIENTS WITH IDIOPATHIC HYPERPROLACTINEMIA

Objective: To investigate the clinical course of hyperprolactinemia without demonstrable cause. Design: Prospective study of all patients with idiopathic hyperprolactinemia first seen between 1974 and 1985. Setting: Outpatient Department of University Hospital. Patients: Fifty-nine patients followed for 6 to 190 months (median 78 months). Medical treatment given only in case of anovulatory infertility or hypogonadism. Outcome Measures: Development of pituitary (micro)prolactinoma, prolactin (PRL) levels, and clinical signs of menstrual dysfunction. Results: With exception of one woman in whom it probably had been missed by hypocycloidal tomography, no demonstrable prolactinoma developed. Prolactin levels rose in two patients, one using oral contraceptives and the other with prolactinoma. At the end of follow-up, 15 of 16 patients using a dopaminergic drug had a normal cycle; 13 had normal final PRL levels. From the 43 patients off medication, 28 (66%) had normal PRL levels and 23 (54%) had a normal cycle. There were no significant differences between women who had and had not been pregnant. Dopaminergic medication had no appreciable influence on the course of the disease. Conclusion: In idiopathic hyperprolactinemia, progression to pituitary prolactinoma seldom, if ever, occurs. There is a high tendency to spontaneous cure, and pregnancy or medication have no apparent effect. Frequent pituitary imaging was found to be not necessary in our patient population. It may best be reserved for situations in which the PRL level in symptomatic hyperprolactinemia is inconsistent with pituitary imaging results

THE EFFECT OF 2 DOPAMINERGIC DRUGS ON MENSTRUAL FUNCTION AND PSYCHOLOGICAL STATE IN HYPERPROLACTINEMIA

Objective: To investigate the effect of dopaminergic drugs on the well being in hyperprolactinemic patients. Design: A psychometric test for well being, the SCL-90, was applied at baseline and in the 24th week of a double-blind randomized prospective study comparing the effectiveness and safety of the new dopamine d2 agonist CV 205-502 with bromocriptine. Setting: Outpatient department of a university clinic for obstetrics and gynecology. Patients: Twenty-four women with hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before, and 11 were known to react unfavorably to bromocriptine. Results: The effectiveness of CV 205-502 was identical to bromocriptine: its tolerability appeared to be better, especially in the initial phase of treatment. At baseline, the mean scores of the SCL-90 were significantly elevated over the reference values. Sixteen patients had normal scores. The elevations were caused by 8 patients with scores in the range found in psychiatric disease (211 +/- 30 [SD] [CV 205-502] and 182 +/- 32 [bromocriptine]). They were depressed, anxious, and hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130 +/- 23.5) in the SCL-90 than the patients treated with bromocriptine (149.5 +/- 20). Conclusion: The markedly increased well being in patients treated with CV 205-502 cannot be explained by its better tolerability and is probably caused by a specific central activity of CV 205-502. Further research into the antidepressive properties of this compound is warranted