Síndrome de insuficiência androgênica: critérios diagnósticos e terapêuticos

A síndrome da insuficiência androgênica na mulher (SIA) desperta, mesmo nos dias atuais, muitas discussões e encerra muitas controvérsias. Sabe-se, no entanto, que os níveis plasmáticos de testosterona declinam progressivamente ao longo do período reprodutivo. Conceitua-se a SIA como o conjunto de sintomas clínicos, a presença de biodisponibilidade diminuída de testosterona e os níveis normais de estrogênios. Entre os principais sintomas, citam-se o comprometimento do bem-estar, o humor disfórico, a fadiga sem causa aparente, o comprometimento do desejo sexual, o emagrecimento e a instabilidade vasomotora em mulheres pós-menopáusicas sob terapêutica estrogênica. Esses sintomas, no entanto, são potencialmente atribuíveis a diferentes etiologias e dificultam o correto diagnóstico na maioria dos casos, ainda que ele seja lembrado com freqüência em pacientes que se submetem à ooforectomia bilateral. O diagnóstico da SIA parece ser essencialmente clínico, não havendo a necessidade das dosagens laboratoriais para a sua comprovação. Não se deve indicar a terapêutica androgênica (TA) em pacientes que não estejam adequadamente estrogenizadas. Considera-se a testosterona o hormônio ideal para a TA. As pacientes com sintomas sugestivos de SIA, excluídas outras causas identificáveis, especialmente se pós-menopáusicas, são candidatas à TA. Não existem dados de segurança sobre a TA em usuárias em longo prazo. A via transdérmica - através de adesivos, cremes e gel - parece ser preferível à oral.

AN EXTREMELY LARGE, CAULIFLOWER-TYPE, CUTANEOUS METASTASIS OF OVARIAN-CANCER ASSOCIATED WITH GOOD PROGNOSIS

We report an unusual case of a 37-year-old woman who presented in 1980 with a serous papillary cystadenocarcinoma of the ovary. The patient refused any treatment and the patient was lost to follow-up for 6 years. After this period of time she returned with an extremely large, cutaneous, cauliflower-type of metastasis located in the lower abdominal wall and measuring 20 x 20 cm. She received two courses of chemotherapy treatment consisting of intraperitoneal cisplatin (100 mg/m2) and intravenous epirubicin (50 mg/m2) every 3 weeks. After the second course of chemotherapy she received cobalt radiotherapy (5000 cGy). Subsequently, she received four more courses of chemotherapy with dramatic remission of the cutaneous metastasis. Shortly after chemotherapy, the patient underwent a laparotomy consisting of the resection of the abdominal wall including the cutaneous metastasis completed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The patient is well after the surgery and without any evidence of residual disease after 6 years of follow up. This description illustrates a rare example of ovarian cancer with skin metastases and favorable outcome. (C) 1994 Academic Press, Inc.

Detecting early biomechanical effects of zoledronic acid on femurs of osteoporotic female rats

Aim. To investigate the biomechanical effects of zoledronic acid (ZA) on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O) (n=40) and sham surgery (S) (n=40). At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW) was intraperitoneally administered: OZA (n=20), ODW (n=20), SZA (n=20), and SDW (n=20). The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N), yield point (N), and stiffness coefficient (N/mm) of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy. © 2012 Evandro Pereira Palacio et al.

Estudo clínico, biomecânico e histológico do efeito da menopausa induzida por ooforectomia no tecido ósseo. Modelo experimental em ratas

Pós-graduação em Bases Gerais da Cirurgia - FMB

Efeitos do ácido zoledrônico sobre o processo de remodelação óssea em ratas ooforectomizadas: estudo clínico, densitométrico, biomecânico e microtomográfico

Pós-graduação em Bases Gerais da Cirurgia - FMB

Incomplete ovariosalpingectomy and subsequent malignant granulosa cell tumor in a female green iguana (Iguana iguana)

Case Description-A 9-year-old spayed female green iguana (Iguana iguana) was evaluated because of a distended coelom and weight loss. History included a single episode of egg binding and subsequent bilateral ovariosalpingectomy.;Clinical Findings-Physical examination revealed a mass within the coelomic cavity. Ultrasonography revealed a large, irregular mass with hypoechoic regions and coelomic effusion. Clinicopathologic derangements included heterophilia, monocytosis, lymphopenia, basophilia, hypocholesterolemia, hypoproteinemia, and hypercalcemia. Results of cytologic evaluation of the mass were suggestive of malignant epithelial neoplasia, but neoplastic cells were not found in the effusion. An ovarian tumor was suspected on the basis of clinical signs, clinicopathologic findings, and results of cytologic evaluation of the mass.;Treatment and Outcome-Surgical exploration revealed a large left ovary, a normal-appearing contralateral ovary, and a mass in the fat body, all of which were removed and submitted for histologic examination. The histologic diagnosis was granulosa cell tumor with metastasis to the fat body. The patient died 11 months after evaluation, and disseminated granulosa cell tumor was confirmed at necropsy; histologic examination at that time also identified systemic mastocytosis.;Clinical Relevance-Granulosa cell tumors are uncommon in reptiles, and this was the first granulosa cell tumor described antemortem cytologically, histologically, and ultrastructurally in an iguana. Findings in this iguana underscored concerns associated with incomplete oophorectomy of iguanas; cytologic and histopathologic findings were similar to those observed in other domestic animals. Oophorectomy should be considered as an alternative to standard ovariosalpingectomy to avoid potential complications in pet reptiles, and use of microsurgical instruments and vascular clips is advised. (J Am Vet Med Assoc 2011239:237-242)

Treatment of premenopausal women with early breast cancer: old challenges and new opportunities

Breast cancer occurring in women before the age of menopause continues to be a major medical and psychological challenge. Endocrine therapy has emerged as the mainstay of adjuvant treatment for women with estrogen receptor-positive tumours. Although the suppression of ovarian function (by oophorectomy, irradiation of the ovaries or gonadotropin releasing factor analogues) is effective as adjuvant therapy if used alone, its value has not been proven after chemotherapy. This is presumably because of the frequent occurrence of chemotherapy-induced amenorrhoea. Tamoxifen reduces the risk of recurrence by approximately 40%, irrespective of age and the ovarian production of estrogens. The worth of ovarian function suppression in combination with tamoxifen is unproven and is being investigated in an intergroup randomised clinical trial (SOFT [Suppression of Ovarian Function Trial]). Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are only being investigated in younger patients. The use of chemotherapies is identical in younger and older patients; however, at present the efficacy of chemotherapy in addition to ovarian function suppression plus tamoxifen is unknown in premenopausal patients with endocrine responsive disease. 'Targeted' therapies such as monoclonal antibodies to human epidermal growth factor receptor (HER)-2, HER1 and vascular endothelial growth factor, 'small molecule' inhibitors of tyrosine kinases and breast cancer vaccines are rapidly emerging. Their use depends on the function of the targeted pathways and is presently limited to clinical trials. Premenopausal patients are best treated in the framework of a clinical trial.

Estrogen receptor modulators and down regulators: optimal use in postmenopausal women with breast cancer

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.

Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

A rare benign ovarian tumour

Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery.

Riscontri istologici in individui transgender AFAB in terapia con testosterone

CONTESTO: Il rischio oncologico dell’esposizione al testosterone (T) di organi genitali in transgender AFAB non è noto. SCOPO: valutazione istologica di utero, cervice, salpingi e ovaia asportati in corso di intervento chirurgico di affermazione di genere (GAS) in AFAB che assumevano testosterone. MATERIALI E METODI: valutazione dei dati istologici condotta retrospettivamente tramite la consultazione di 187 cartelle cliniche di soggetti transgender AFAB sottoposti a GAS presso la Ginecologia dell’IRCCS Sant’Orsola, Bologna. RISULTATI: 187 transgender AFAB sono stati sottoposti a isteroannessiectomia bilaterale. Nessun paziente sottoposto a ovariectomia, chemioterapia o radioterapia prima della chirurgia. La mediana della durata di assunzione di T era di 36 mesi (12 mesi-14 anni). 96/187 (51.4%) uteri presentavano endometrio ipoattivo/atrofico, mentre 1 caso di iperplasia senza atipie cellulari è stato identificato (0.5%), 8/187 (4.3%) endometrio polipoide e 4/187 (2.2%) secretivo. Il più comune riscontro istologico cervicale è stata la cervicite cronica (n=174, 93%) associata a metaplasia (n=131,76%). Le salpingi sono risultate indenni in 90/187 (48.1%) casi e con infiammazione cronica in 91/187 (48,7%) casi. La maggior parte delle ovaie analizzate mostravano follicoli in diversi stati di maturazione (n=117, 62.5%). In 20 analisi istologiche sono stati identificati corpi lutei/corpi lutei emorragici (10.7%). CONCLUSIONI: Nessuna lesione premaligna o maligna è stata riscontrata in questi 187 soggetti che assumevano testosterone fino a un massimo di 168 mesi prima della chirurgia. La presenza di follicoli in vari stadi di sviluppo e di corpi lutei suggerisce la possibilità di cicli ovulatori in corso di terapia con testosterone. I risultati di questo studio confermano la sicurezza dell'uso prolungato di T sugli organi genitali di transgender AFAB. Seppur ancora limitate, le evidenze suggeriscono sempre più la mancanza di necessità assoluta di rimuovere utero e ovaia nei soggetti trasgender in terapia con T con il solo fine di prevenire patologie oncologiche.