Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

A Systematic Review of Systematic Reviews on the Use of Aromatase Inhibitors for the Treatment of Endometriosis: The Evidence to Date.

Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950-2022), Google Scholar (2004-2022), Cochrane Library (2010-2022) and Researchgate (2010-2022). The search included the following medical subject headings (MeSH) or keywords: "Aromatase Inhibitors" AND "Endometriosis" AND "Systematic reviews" OR "Systematic review" AND "Reviews" OR "Reviews" AND "Endometriosis". The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy.

Identification of Non-steroidal Aromatase Inhibitors via In silico and In vitro Studies

INTRODUCTION: Breast cancer is the most common cancer affecting women worldwide, including Pakistan. More than half of breast cancer patients have hormone-dependent breast cancer, which is developed due to the over-production of estrogen (the main hormone in breast cancer). METHOD: The biosynthesis of estrogen is catalyzed by the aromatase enzyme, which thus serves as a target for the treatment of breast cancer. During the current study, biochemical, computational, and STD-NMR methods were employed to identify new aromatase inhibitors. A series of phenyl-3- butene-2-one derivatives 1-9 were synthesized and evaluated for human placental aromatase inhibitory activity. Among them, four compounds 2, 3, 4, and 8 showed a moderate to weak inhibitory activity (IC50 = 22.6 - 47.9 µM), as compared to standard aromatase inhibitory drugs, letrozole (IC50 = 0.0147 ± 1.45 µM), anastrozole (IC50 = 0.0094 ± 0.91 µM), and exemestane (IC50 = 0.2 ± 0.032 µM). Kinetic studies on two moderate inhibitors, 4 and 8, revealed a competitive- and mixed-type of inhibition, respectively. RESULT: Docking studies on all active compounds indicated their binding adjacent to the heme group and interaction with Met374, a critical residue of aromatase. STD-NMR further highlighted the interactions of these ligands with the aromatase enzyme. CONCLUSION: STD-NMR-based epitope mapping indicated close proximity of the alkyl chain followed by an aromatic ring with the receptor (aromatase). These compounds were also found to be non-cytotoxic against human fibroblast cells (BJ cells). Thus, the current study has identified new aromatase inhibitors (compounds 4, and 8) for further pre-clinical and clinical research.

BMX controls 3ßHSD1 and sex steroid biosynthesis in cancer.

Prostate cancer is highly dependent on androgens and the androgen receptor (AR). Hormonal therapies inhibit gonadal testosterone production, block extragonadal androgen biosynthesis, or directly antagonize AR. Resistance to medical castration occurs as castration-resistant prostate cancer (CRPC) and is driven by reactivation of the androgen-AR axis. 3ß-hydroxysteroid dehydrogenase-1 (3ßHSD1) serves as the rate-limiting step for potent androgen synthesis from extragonadal precursors, thereby stimulating CRPC. Genetic evidence in men demonstrates the role of 3ßHSD1 in driving CRPC. In postmenopausal women, 3ßHSD1 is required for synthesis of aromatase substrates and plays an essential role in breast cancer. Therefore, 3ßHSD1 lies at a critical junction for the synthesis of androgens and estrogens, and this metabolic flux is regulated through germline-inherited mechanisms. We show that phosphorylation of tyrosine 344 (Y344) occurs and is required for 3ßHSD1 cellular activity and generation of Δ4, 3-keto-substrates of 5α-reductase and aromatase, including in patient tissues. BMX directly interacts with 3ßHSD1 and is necessary for enzyme phosphorylation and androgen biosynthesis. In vivo blockade of 3ßHSD1 Y344 phosphorylation inhibits CRPC. These findings identify what we believe to be new hormonal therapy pharmacologic vulnerabilities for sex-steroid dependent cancers.

The Role of Aromatase Enzyme in Hormone Related Diseases and Plant- Based Aromatase Inhibitors as Therapeutic Regimens.

Medicinal plants have a long history of use as food and remedy in traditional and modern societies. They have been used as herbal drugs and sources of novel bioactive compounds. They provide a wide array of chemical compounds, many of which can not be synthesized via current synthesis methods. Natural products may provide aromatase inhibitory activity through various pathways and may act clinically effective for treating pathologies associated with excessive aromatase secretion, including breast, ovarian, and endometrial cancers, endometriosis, uterine fibroid, benign prostatic hyperplasia (BPH), prostate cancer, infertility, and gynecomastia. Recent studies have shown that natural products with aromatase inhibitory activity can also be good options against secondary recurrence of breast cancer by exhibiting chemopreventive effects. Therefore, screening for new plant-based aromatase inhibitors may provide novel leads for drug discovery and development, particularly with increased clinical efficacy and decreased side effects.

Use of aromatase inhibitors in menopausal deep endometriosis: a case report and literature review.

We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities.

Placental aromatase expression decreased in severe neonatal opioid withdrawal syndrome.

Background: Severe neonatal opioid withdrawal syndrome (NOWS) cannot be predicted. Placental aromatase metabolizes both methadone and buprenorphine and may contribute to the severity of NOWS.Objectives: To determine whether placental aromatase mRNA expression differs in methadone- or buprenorphine-exposed placentas and is associated with NOWS severity.Study design: Prospective multicenter observational cohort study from July 2016 to December 2017. Inclusion: pregnant, ≥18 years old, singleton fetus, nonanomalous, ≥34 weeks at delivery, documented methadone or buprenorphine use. Exclusion: declined sample collection. Severe NOWS is defined as three consecutive Finnegan scores ≥8 or sum of three consecutive scores ≥24 within 72 hours of birth. Finnegan scoring was correlated with placental mRNA expression and compared to umbilical cord drug and metabolite levels. Data were analyzed using descriptive, parametric, and nonparametric statistics and regression analysis. p-Value <.05 was considered significant.Results: Thirty-eight out of 45 (84%) patients were included. Methadone and buprenorphine were used by 29/38 (76%) and 9/38 (24%) of patients, respectively. 19/38 (50%) infants had severe NOWS. Placental aromatase/actin mRNA expression was significantly lower in the placentas of infants with severe NOWS (p = .04). Mean umbilical cord 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)/methadone ratios were significantly higher in infants with severe NOWS (p = .03). Placental aromatase mRNA expression was weakly to moderately correlated with umbilical cord methadone, buprenorphine, and their metabolite concentrations (r = 0.4-0.8).Conclusion: Placental aromatase mRNA expression was lower and umbilical cord EDDP/methadone ratios were higher in infants with severe NOWS. Additional investigation of placental aromatase in methadone- and buprenorphine-exposed pregnancies is needed.

Targets in anticancer research--A review.

Cancer is a complex disease characterized by a loss in the normal cell regulatory mechanisms that govern cell survival, proliferation, and differentiation. Current chemotherapeutics, as anticancer agents, are developing resistance to single drug and also to treatment therapies involving multiple drugs. Cross resistance associated with the specificity and selectivity of existing drugs has restricted the application of chemotherapy. Alternatively, these limitations have given better insight in understanding the underlying molecular mechanisms responsible for the development of various stages in cancer. In the light of this, continuous efforts are being made in order to identify and validate newer anticancer targets. This review presents some of the important targets that have been already reported, such as aromatase, farnesyl transferase, histone deacetylase, tyrosine kinase and cyclin-dependent kinase. A few molecules designed against these targets have successfully reached clinical trials. However, only limited marketed drugs are available from these classes. Besides, the review also highlights some of the other important targets and strategies that have also drawn considerable attention in the area of anticancer drug development such as, cancer stem cells and monoclonal antibodies. Further, the integration of the tools in molecular biology with the results from preclinical and clinical trials would strengthen the effectiveness of treatment regimens in cancer patients. There lies a much scope for designing promising lead compounds and treatment therapies against these established targets.

Cáncer de mama en el varón: revisión de la literatura y aportación de nuestra casuística / No disponible

Objetivos: Revisar los perfiles inmunohistoquímicos, aspectos genéticos y hormonales ligados a la expresión de tumores, factores pronósticos y tratamientos hormonales como inhibidores de la aromatasa en el cáncer de mama en el varón. Así mismo aportar nuestra casuística. Métodos: Se realizó una búsqueda bibliográfica utilizando las palabras clave cáncer de mama, varón, clasificación molecular e inmunohistoquímica en los repertorios bibliográficos de Pubmed y Tripdatabase entre los años 2001-2011. Así mismo hemos realizado un estudio retrospectivo de los varones que han sido diagnosticados e intervenidos quirúrgicamente por cáncer de mama en nuestro hospital en los últimos 15 años. Conclusiones: La clasificación según los marcadores inmunohistoquímicos del cáncer de mama permitiría distinguir aquellos con mejor y peor pronóstico, siendo el más favorable el tipo luminal A y sienta las bases del tratamiento tanto neo como adyuvante(AU)

Objectives: To review the immunohistochemical profiles, genetic and hormonal aspects linked to the expression of tumors, prognosis factors and hormonal treatments, like aromatase inhibitor, in male breast cancer. Also, to report our casuistry. Methods: A bibliographic review using the keywords breast cancer, male, molecular and immunohistochemical classification was carried out on PubMed and Tripdatabase between 2001 and 2010. Also, we made a retrospective study of male patients with breast cancer diagnosed and treated in our hospital within the last 15 years. Conclusions: The classification of breast cancer in male patients according to immunohistochemical markers would permit to distinguish between tumors with good or bad prognosis, being the luminal A type the most favourable, and assess the basis of neodjuvant and adjuvant treatment(AU)

Carcinoma de células fusiformes tipo “fibromatosis-like”: una variante inusual de carcinoma metaplásico de mama asociado a carcinoma ductal / No disponible

El carcinoma de células fusiformes tipo fibromatosis-like esuna variante del carcinoma metaplásico, que ha sido reconocidorecientemente como una entidad distinta e independiente del restode los tumores metaplásicos, que recuerda a la fibromatosis yse caracteriza por ser un tumor de bajo grado, con mejor pronósticoy tendencia a la recidiva local. Presentamos un caso de unapaciente de 71 años con un carcinoma tipo fibromatosis-likeasociado a un carcinoma ductal de la mama. La histología revelóun tumor de células fusiformes simulando una fibromatosis, dondese puede identificar un componente epitelial en forma de carcinomaductal o intraductal en continuidad con el componente deaspecto fusiforme. Inmunohistoquímicamente presentó positividadfocal para marcadores epiteliales y mioepiteliales como citoqueratinasy expresión de marcadores mesenquimales como vimentina.El diagnóstico exacto puede presentar dificultad tantoradiológica como anatomopatológica y plantea el diagnóstico diferencialcon lesiones benignas como fibromatosis, fascitis nodularo malignas como sarcomas. El comportamiento y pronósticono ha sido del todo aclarado aunque se ha visto que es un tumorque se caracteriza por un alto riesgo de recidiva, bajo potencialpara metastatizar en ganglios linfáticos regionales pero con capacidadpara producir metástasis a distancia y por tanto, debería sertratado en consecuencia(AU)

Fibromatosis-like spindle cell carcinoma of the breast is avariant of metaplastic carcinoma that has recently been recognizedas a different entity because of its resemblance to fibromatosisand similar propensity for local recurrence. We presenta case of 71- year-old lady with a fibromatosis-like carcinomaassociated with ductal carcinoma of the breast. Finalhistology revealed a tumor with predominant spindle cells in acollagenous background, simulating a fibromatosis. Inmunohistochemistryshowed focal positivity of ephithelial and myoephitelialmarkers as citokeratins and expression of mesenchymalmarker as vimentin in the tumor. This tumor can posediagnostic difficulty radiologic as histopathology and the differentialdiagnosis includes both benign and malignant spindlecell breast lesions as a fibromatosis, nodule fascitis or sarcomas.The behaviour and prognosis have not been well clarifiedalthough there seems to have high risk of local recurrence, lowpotential to metastasize to regional lymph nodes and potentialfor distant metastasis and should be treated accordingly(AU)

Quimioprevenção do câncer de mama / Current status of breast cancer chemoprevention

Quimioprevenção é definida como o uso de agentes químicos naturais ou sintéticos para reverter, suprimir ou prevenir a progressão carcinogênica para carcinoma invasor. Os fármacos que agem como agentes quimiopreventivos contra o câncer de mama são divididos em dois grupos principais: os que previnem cânceres de mama receptor de estrogênio (RE) positivos, como os moduladores seletivos do receptor de estrogênio (SERM), inibidores de aromatase, agonistas de GnRH e fitoestrogênios; e os fármacos que previnem os cânceres RE-negativos, como os inibidores da ciclooxigenase-2 (COX-2), retinóides, as estatinas, os inibidores do receptor tirosina quinase, o anticorpo monoclonal contra HER-2 e os inbidores da telomerase. Resultados do estudo conduzido pelo NSABP que comparou o tamoxifeno com o raloxifeno (STAR), avaliando a eficácia na redução de risco, assim como a toxicidade desses dois SERMs em uma população similar e de alto risco para câncer de mama, demonstrou que o raloxifeno é tão efetivo quanto o tamoxifeno na redução de risco de câncer de mama invasor (p=0,83) e apresentou menor risco de eventos tromboembólicos e catarata; todavia, exibiu maior risco de carcinoma não invasor, porém sem significância estatística. Baseado nos dados promissores que revelaram diminuição de risco de câncer de mama contralateral em estudos de adjuvância, alguns inibidores de aromatase, incluindo o letrozol, anastrazol e exemestane, estão sendo incorporados em investigações para avaliar sua eficácia como agentes preventivos de alto risco em mulheres. Os inibidores de COX-2 demonstraram sua eficácia na prevenção do câncer de mama em estudos caso-controle e coorte, sendo necessários estudos aleatórios para atestar sua eficácia. O resultado positivo de alguns ensaios clínicos na prevenção do câncer de mama em populações de alto risco sugere que a quimioprevenção é uma estratégia racional e atraente.

Chemoprevention is defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER) - positive breast cancers [selective estrogen receptor modulators (SERM), aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER - negative breast cancers [cyclooxygenase-2 (COX-2) inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR), which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83). It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy.

[Current status of breast cancer chemoprevention]. / Quimioprevenção do câncer de mama.

Chemoprevention is defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER)-positive breast cancers [selective estrogen receptor modulators (SERM), aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER-negative breast cancers [cyclooxygenase-2 (COX-2) inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR), which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83). It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy.

El exemestano, un inhibidor de aromatasa, nueva opción en el tratamiento del cáncer de mama / Exemestano, an aromatase inhibitor, a new option in the treatment of breast cancer

El exemestano, un inhibidor de aromatasa, se convierte en una nueva esperanza para muchas mujeres con cáncer de mama, al evitar la reaparición de tumores de forma más efectiva que el tamoxifeno, medicamento que actualmente se usa en primera línea como terapia hormonal para combatir esta enfermedad, en un ensayo clínico, aleatorizado y a doble ciego, que involucró a 4 742 pacientes de 37 países.1,2El estudio fue coordinado por el Imperial College London, bajo los auspicios del Breast International Group y patrocinado por el consorcio farmacéutico Pfizer, actual propietario del Aromasin, nombre comercial del exemestano, obtenido originalmente por la empresa Pharmacia(AU)

[Chemoprevention of breast cancer. Clinical trials in pharmacological prevention]. / Quimioprevención del cáncer de mama. Ensayos clínicos en la prevención farmacológica.

The following review article focuses on chemoprevention clinical trials of breast cancer. To date, SERMs (Selective Estrogen Receptor Modulators) have been the most studied drugs. Four randomized trials with tamoxifen vs. placebo have been performed and two with raloxifene are being carried out. Two tamoxifen trials showed between 30 and 50% reduction in breast cancer incidence. However, two other studies showed no statistical differences. Moreover, the real impact on mortality that these therapies could have is still unknown. This article includes a revision of trials that evaluated the relationship between daily vitamin intake and breast cancer. A follow up of these trials will give us answers about which patients will benefit from chemoprevention therapies.

Quimioprevencion del cancer de mama: ensayos clinicos en la prevencion farmacologica / Chemoprevention of breast cancer: clinical trials in pharmacological prevention

El presente artículo trata sobre los ensayos clínicos presentados en quimioprevención del cáncer mamario. Hasta la fecha las drogas más estudiadas han sido los Moduladores Selectivos de los Receptores de Estrógenos (SERMs). Cuatro estudios aleatorizados de tamoxifeno versus placebo fueron publicados y dos con raloxifeno están en curso. Dos de los estudios con tamoxifeno mostraron una reducción de incidencia de cáncer mamario entre el 30 y el 50%, sin embargo otros dos trabajos no mostraron diferencias estadísticamente significativas. A esta controversia se le suma la incertidumbre sobre el verdadero impacto en la mortalidad que pudiera tener este tipo de terapia preventiva. Se citan además diversos estudios que evaluaron la ingesta de vitaminas y su relación con el desarrollo de tumores mamarios. Sin duda alguna el estudio y el seguimiento de los ensayos clínicos nos permitirán dilucidar qué pacientes requieren una terapia, preventiva del desarrollo de un tipo específico de cáncer, que se encuentra lejos de estar exenta de riesgos.

Quimioprevencion del cancer de mama: ensayos clinicos en la prevencion farmacologica / Chemoprevention of breast cancer: clinical trials in pharmacological prevention

El presente artículo trata sobre los ensayos clínicos presentados en quimioprevención del cáncer mamario. Hasta la fecha las drogas más estudiadas han sido los Moduladores Selectivos de los Receptores de Estrógenos (SERMs). Cuatro estudios aleatorizados de tamoxifeno versus placebo fueron publicados y dos con raloxifeno están en curso. Dos de los estudios con tamoxifeno mostraron una reducción de incidencia de cáncer mamario entre el 30 y el 50%, sin embargo otros dos trabajos no mostraron diferencias estadísticamente significativas. A esta controversia se le suma la incertidumbre sobre el verdadero impacto en la mortalidad que pudiera tener este tipo de terapia preventiva. Se citan además diversos estudios que evaluaron la ingesta de vitaminas y su relación con el desarrollo de tumores mamarios. Sin duda alguna el estudio y el seguimiento de los ensayos clínicos nos permitirán dilucidar qué pacientes requieren una terapia, preventiva del desarrollo de un tipo específico de cáncer, que se encuentra lejos de estar exenta de riesgos. (AU)

Aromatase inhibition for the treatment of idiopathic hypogonadotropic hypogonadism in men with premature ejaculation.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) has been observed to occur in men with premature ejaculation (PE). Common IHH therapies include testosterone replacement, which increases testosterone levels but suppresses gonadotropin release; and gonadotropin-releasing hormone supplementation, which restores gonadotropin levels but is impractical for chronic use. Hormonal imbalances associated with IHH/PE are thought to be related to hyperactivity of the cytochrome P-450 enzyme aromatase. METHODS: Ten male patients with a diagnosis of IHH/PE were treated with the aromatase inhibitor anastrazole (1 mg/d orally). Levels of free and total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol were determined at baseline and after 2 weeks of therapy. RESULTS: After 2 weeks of therapy with anastrazole, levels of testosterone, luteinizing hormone, and estradiol had returned to normal. No effect was noted on premature ejaculation. CONCLUSION: These results suggest that aromatase inhibition with anastrazole may provide a practical and efficacious alternative for the treatment of IHH but is not effective in preventing premature ejaculation.