RESUMEN
OBJECTIVE: Because of the expected increase in the number of dementia patients, the unlikelihood of a cure in the near future, and the rising cost of care, there is an increasing need for effective caregiver interventions. Internet interventions hold considerable promise for meeting the educational and support needs of informal dementia caregivers at reduced costs. The current study aims to provide an overview of the evidence for the effectiveness, feasibility, and quality of Internet interventions for informal caregivers of people with dementia. METHODS: A systematic literature search of five scientific databases was performed, covering literature published up to 10 January 2013. Twelve studies were identified. The quality of the included studies was assessed according to the Cochrane level of evidence and the criteria list of the Cochrane Back Review Group. RESULTS: The intervention types, dosage, and duration differed widely, as did the methodological quality of the included studies. The overall level of evidence was low. However, the results demonstrate that Internet interventions for informal dementia caregivers can improve various aspects of caregiver well-being, for example, confidence, depression, and self-efficacy, provided they comprise multiple components and are tailored to the individual. Furthermore, caregivers could benefit from interaction with a coach and other caregivers. CONCLUSIONS: Internet interventions for informal dementia caregivers may improve caregiver well-being. However, the available supporting evidence lacks methodological quality. More randomized controlled studies assessing interventions performed according to protocol are needed to give stronger statements about the effects of supportive Internet interventions and their most promising elements.
Asunto(s)
Cuidadores/psicología , Consejo , Demencia/enfermería , Internet , Apoyo Social , Consejo/métodos , Demencia/psicología , Humanos , Educación del Paciente como Asunto/métodosRESUMEN
The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess, specific identifiable disorders (NCAH, CAH, HAIRAN syndrome, and androgen-secreting neoplasms) were observed in approximately 7% of subjects, whereas functional androgen excess, principally PCOS, was observed in the remainder. Hirsutism, menstrual dysfunction, or acne, but not alopecia, improved in the majority of patients treated with a combination suppressive therapy; although more than 60% experienced side effects.
Asunto(s)
Acantosis Nigricans/complicaciones , Hiperplasia Suprarrenal Congénita/complicaciones , Andrógenos/metabolismo , Neoplasias de las Glándulas Endocrinas/complicaciones , Neoplasias de las Glándulas Endocrinas/metabolismo , Hiperandrogenismo/etiología , Acantosis Nigricans/epidemiología , Hiperplasia Suprarrenal Congénita/epidemiología , Adulto , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de las Glándulas Endocrinas/epidemiología , Femenino , Humanos , Hiperandrogenismo/tratamiento farmacológico , Prevalencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Polycystic ovary syndrome is the most common cause of oligo-ovulation, affecting approximately 4% of women. A primary defect of steroidogenesis resulting in increased ovarian and adrenal androgen production may be responsible for polycystic ovary syndrome, at least in some patients. Because the action of the steroidogenic acute regulatory protein (StAR) initiates the process of steroidogenesis, we proceeded to test the hypothesis that increased production or concentration of StAR may result in the abnormality of steroidogenesis found in polycystic ovary syndrome. STUDY DESIGN: We examined the ovaries from 10 healthy women and 7 women with polycystic ovary syndrome, determining the relative concentration of StAR in total protein extracts by use of Western blotting, and the overall distribution and staining intensity of StAR in prepared tissue sections. RESULTS: Overall the ovaries of healthy women and women with polycystic ovary syndrome demonstrated a similar prevalence and size of follicular cysts, although the ovaries of women with polycystic ovary syndrome had a greater mean number of follicular cysts. In general, the distribution of StAR immunoreactivity within most of the ovarian structures was not different in the ovaries of women with polycystic ovary syndrome compared to those of the healthy ovaries. However, the ovaries from the cases demonstrated a significantly greater number of follicular cysts with staining for StAR immunoreactivity in the thecal cells than did the ovaries from healthy women (100% vs 38%, P <.05). CONCLUSION: These data suggest that the exaggeration in androgen biosynthesis in the ovaries of patients with polycystic ovary syndrome may be occurring at its earliest step (ie, that involving StAR), such that an increased amount of cholesterol is made available for androgen biosynthesis in the polycystic ovary.
Asunto(s)
Ovario/metabolismo , Fosfoproteínas/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Western Blotting , Femenino , Humanos , Inmunohistoquímica/métodos , Ovario/citología , Ovario/patología , Síndrome del Ovario Poliquístico/patología , Valores de Referencia , Coloración y Etiquetado , Células Tecales/metabolismoRESUMEN
OBJECTIVE: To determine the effect of repeated freezing and thawing, and storage temperature, on the assay results of commonly measured reproductive hormones, and sex hormone-binding globulin (SHBG) in human serum. DESIGN: Prospective laboratory study. SETTING: Academic medical center. PATIENT(S): Four men and three pregnant women in the third trimester. INTERVENTION(S): Pooled serum from men and pregnant females were frozen at either -20 degrees C or -70 degrees C. Aliquots were then subjected to repeat freeze/thaw cycles, from 1 to 10 times, and assays were performed after the final freeze/thaw cycle. MAIN OUTCOME MEASURE(S): Assay results for eight hormones (FSH, LH, PRL, androstenedione (A), 17alpha-hydroxyprogesterone, P, insulin, and SHBG, as a function of the number of freeze/thaw cycles and storage temperature. RESULT(S): Only SHBG in male serum at -20 degrees C and P in pregnant serum at -70 degrees C showed statistically significant decreases in assay results with repeated freeze/thaw cycles (3.3% and 1.1% per cycle, respectively). All other analytes did not show significant changes as a function of freeze/thaw cycles or storage temperature. CONCLUSION(S): There is no consistent or predictable alteration in the results of SHBG, or the glycoprotein and steroid hormones evaluated, as a function of repeated freeze/thaw or the storage temperature of human serum.
Asunto(s)
Congelación , Hormonas/sangre , Reproducción/fisiología , Conservación de la Sangre , Criopreservación , Femenino , Humanos , Masculino , Embarazo , Estudios Prospectivos , Globulina de Unión a Hormona Sexual/análisis , TemperaturaRESUMEN
Excess adrenal androgen (AA) levels are observed in 25--50% of women with the polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent selection bias. Thus, it is possible that AA secretion among the general population is highly variable, and that those women who are predisposed to secreting greater amounts of AA have a greater probability of having PCOS. We now hypothesize that the levels of AAs are highly variable among normal nonhyperandrogenic women, and that this heterogeneity is the result of a variable response of AAs to ACTH stimulation. To test this hypothesis we prospectively studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1--24) in 56 healthy eumenorrheic nonhirsute healthy women with a mean age of 28.9 yr (range, 20--37 yr.) and a mean body mass index (BMI) of 29.2 kg/m(2) (18.2--46.2 kg/m(2)). Baseline samples and poststimulation samples were assayed for DHA and F. The basal and ACTH-stimulated levels of DHA, but not those of F, were negatively correlated with age, although neither the basal nor ACTH-stimulated responses of DHA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. Delta F; r = -0.54; P < 0.001), whereas there was no significant relationship between basal DHA and Delta DHA. We also compared the intersubject variability (coefficient of variation) for basal and stimulated levels of DHA and F. For basal (DHA(0)), 60 min (DHA(60)), and net increment in (Delta DHA) DHA levels, the coefficients of variation were 67.9%, 61.4%, and 76.0%, respectively; for F(0), F(60), and Delta F, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in Delta DHA was significantly higher, and the variance in F(60) was significantly lower than that in all other variables; DHA(0), DHA(60), F(0), and Delta F had similar variances. In conclusion, in our population of healthy reproductive-aged women we observed that both basal and ACTH-stimulated levels of DHA after ACTH-(1--24) stimulation had significantly greater intersubject variance (approximately 60--70%) compared with the basal and poststimulation levels of F (approximately 15--40%). These data support the hypothesis that among normal women, AA (i.e. DHA) levels are highly variable compared to those of F. In addition, the intersubject variability in DHA levels is at least in part due to a variable response of AAs to ACTH stimulation. Whether the AA excess frequently observed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.
Asunto(s)
Corteza Suprarrenal/metabolismo , Cosintropina/farmacología , Deshidroepiandrosterona/metabolismo , Deshidroepiandrosterona/sangre , Femenino , Humanos , Hidrocortisona/sangre , Valores de ReferenciaRESUMEN
OBJECTIVE: To determine whether acne is associated with hyperandrogenemia, regardless of age of presentation. DESIGN: Prospective controlled study. SETTING: Tertiary-care medical center. PATIENT(S): Thirty consecutive unselected women presenting with acne and no hirsutism and 24 eumenorrheic healthy controls. INTERVENTION(S): Serum samples was taken in all patients, and an acute 60-minute ACTH-(1-24) test was performed in 19 patients. MAIN OUTCOME MEASURE(S): Total and free T, sex hormone-binding globulin (SHBG), and DHEAS levels in basal samples, and ACTH-stimulated 17-hydroxyprogesterone (17-HP) response to exclude 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) were determined. RESULT(S): Nonhirsute patients with acne demonstrated significantly lower levels of SHBG and higher free-T and DHEAS levels than controls. Nineteen (63%) acneic patients had at least one androgen value above the 95% of controls. In patients aged 12-18 years, 7/8 (88%) had at least one increased androgen value, compared with 12/22 (55%) patients aged 19-43 years. One patient (5.3%) was found to have 21-OH-deficient NCAH. CONCLUSION(S): Hyperandrogenemia was evident in a majority of nonhirsute acneic patients studied, regardless of age. These data suggest that androgen suppression may be useful in treating acne in many of these patients.
Asunto(s)
Acné Vulgar/complicaciones , Andrógenos/sangre , Hiperandrogenismo/complicaciones , 17-alfa-Hidroxiprogesterona/sangre , Acné Vulgar/sangre , Adolescente , Hormona Adrenocorticotrópica/farmacología , Adulto , Niño , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Hiperandrogenismo/sangre , Estudios Prospectivos , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangreRESUMEN
OBJECTIVE: To determine the rate of clinically evident polycystic ovary syndrome (PCOS) among first-degree female relatives within families with a proband affected by PCOS. DESIGN: Clinical and biochemical evaluation of the mothers and sisters of 93 patients with PCOS. The diagnosis of PCOS was established by: [1] a history of oligomenorrhea, [2] clinical evidence (i.e., hirsutism) or biochemical evidence (i.e., elevated total or free T) of hyperandrogenism, and [3] the exclusion of related disorders. SETTING: Tertiary care university. PATIENT(S): Patients with PCOS and their mothers and sisters. INTERVENTION(S): Interview, physical examination, and hormonal testing on blood samples were performed for all subjects. MAIN OUTCOME MEASURE(S): The presence of hirsutism and hyperandrogenemia was determined in the mothers and sisters of the patients with PCOS. RESULT(S): Of the 78 mothers and 50 sisters evaluated clinically, 19 (24%) and 16 (32%) were affected with PCOS, respectively. A higher rate of PCOS was observed when only premenopausal women not taking hormones (i.e., untreated) were considered (i.e., 35% of mothers and 40% of sisters), consistent with amelioration of symptoms with hormonal therapy or aging. These rates of PCOS are significantly higher than that observed in our general population (approximately 4%) and suggest the involvement of a major genetic component in the disorder. CONCLUSION(S): The rates of PCOS in mothers and sisters of patients with PCOS were 24% and 32%, respectively, although the risk was higher when considering untreated premenopausal women only.
Asunto(s)
Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/genética , Adolescente , Adulto , Femenino , Hirsutismo/epidemiología , Hirsutismo/etiología , Humanos , Hiperandrogenismo/epidemiología , Hiperandrogenismo/etiología , Persona de Mediana Edad , Oligomenorrea/epidemiología , Oligomenorrea/etiología , Síndrome del Ovario Poliquístico/complicaciones , Estudios Prospectivos , Testosterona/sangreRESUMEN
OBJECTIVE: To test the hypothesis that patients with nonclassic adrenal hyperplasia (NCAH) exhibit a generalized exaggeration in their response to ACTH stimulation that favors the normal production of F. Patients with 21-hydroxylase (21-OH)-deficient NCAH do not demonstrate cortisol (F) deficiency. DESIGN: Prospective controlled study. SETTING: Tertiary university clinic. PATIENT(S): Twenty-four untreated patients with NCAH diagnosed by a 17 alpha-hydroxyprogesterone (17-HP) level of >30.3 nmol/L (>10 ng/mL), and 37 age- and body mass-matched healthy eumenorrheic nonhirsute controls. INTERVENTION(S): All study subjects underwent a 60 minute acute stimulation using 0.25 mg of ACTH-(1-24) i.v. MAIN OUTCOME MEASURE(S): Basal and stimulated serum levels of pregnenolone (PREG), 17-hydroxypregnenolone (17-HPREG), dehydroepiandrosterone (DHA), progesterone (P4), 17-HP, androstenedione (A4), 11-deoxycortisol (S), and cortisol (F). RESULT(S): The median basal (i.e., Steroid(0)) or ACTH-stimulated (i. e., Steroid(60)) serum levels of PREG, 17-HPREG, DHA, P4, 17-HP, A4 and, most importantly, S were higher in NCAH patients than in controls. In contrast, the levels of F at either 0 minute or 60 minutes of stimulation were similar between NCAH and control women. The proportion of NCAH patients with stimulated steroids levels of >the 95th percentile of controls were as follows: 84.21% for PREG(60), 87.5% for 17-HPREG(60), 95.8% for DHA(60), 89.5% for P4(60), 100% for 17-HP(60), 91.7% for A4(60), 29.2% for S(60), and 4. 1% for F(60). CONCLUSION(S): A generalized adrenocortical hyperresponsivity to ACTH stimulation seems to be present in patients with 21-OH-deficient NCAH, with an exaggerated production of S evident in approximately 30%. The excess production of S in these NCAH patients may, in part, account for their normal F production.
Asunto(s)
Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/metabolismo , Hormona Adrenocorticotrópica/farmacología , Hidrocortisona/metabolismo , Esteroide 21-Hidroxilasa/efectos de los fármacos , 17-alfa-Hidroxipregnenolona/sangre , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Adulto , Androstenodiona/sangre , Estudios de Casos y Controles , Cortodoxona/sangre , Deshidroepiandrosterona/sangre , Femenino , Hirsutismo/metabolismo , Humanos , Pregnenolona/sangre , Progesterona/sangre , Estudios Prospectivos , Esteroide 21-Hidroxilasa/genéticaRESUMEN
We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal androgen deficiency in elderly women. To this end, we quantified basal morning concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and androstenedione (A4) and then evaluated the effects of overnight dexamethasone (DEX) suppression followed by adrenal responses to graded hourly infusions of ACTH, ranging from 20-1280 ng/1.5 m2 x h. Finally, we performed a standard 0.25-mg ACTH bolus stimulation test, with sampling at 1 h thereafter. Basal serum levels of DHEA, DS, and A4 were significantly reduced (approximately 50% each) in a group of 35 healthy postmenopausal women, 55-68 yr old, compared to those in 30 healthy, regularly menstruating women, 20-25 yr old. Post-DEX levels of these C19 steroids also were significantly lower in the older women than in the younger women; the percent decrease after DEX for A4 was greater in the older women, whereas those in DHEA and DS were not age related. Basal and post-DEX levels of F were similar in both groups. Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate. The maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women; those of A4 were similar in both age groups, and the maximally achieved levels of F were higher in the older women than in the younger women. The sensitivity of adrenal DHEA, A4, and F to ACTH (defined as the minimal dose of ACTH required to significantly increase the steroid levels above basal post-DEX values) was similar in older and younger women. The responsiveness of the steroids of interest to ACTH (defined as the slope of the dose-response curve over the linear portion of the dose-response curve) also was similar among younger and older women. These data demonstrate that the deficiency in adrenal androgen production in women is restricted to the delta5-pathway steroid products (DHEA and DS), whereas there is no reduction in the capacity of the adrenal to produce A4 or cortisol. As DHEA and DS are likely to be produced mainly in the zona reticularis of the adrenal cortex, we propose that these data point to an alteration in that cortical zone as the cause of adrenal androgen deficiency in aging. The reductions in A4 in aging are probably due to reduced ovarian secretion after menopause.
Asunto(s)
Glándulas Suprarrenales/fisiología , Hormona Adrenocorticotrópica/farmacología , Envejecimiento/fisiología , Andrógenos/metabolismo , Hidrocortisona/sangre , Posmenopausia/metabolismo , Premenopausia/metabolismo , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Adulto , Anciano , Androstenodiona/sangre , Índice de Masa Corporal , Deshidroepiandrosterona/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad , Pruebas de Función Adreno-Hipofisaria , Estimulación QuímicaRESUMEN
OBJECTIVE: To determine the sensitivity of 11beta-hydroxyandrostenedione (11-OHA4) and delta5-androstenediol (ADIOL) as markers of excessive adrenal androgen production. DESIGN: Prospective study. SETTING: Academic medical centers. PATIENT(S): Thirteen women with untreated 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) and 18 healthy, eumenorrheic, nonhirsute controls matched for age and body mass index. INTERVENTION(S): All subjects were studied before and after acute adrenal stimulation with 0.25 mg of IV ACTH-(1-24). MAIN OUTCOME MEASURE(S): Basal levels of total testosterone, sex hormone-binding globulin, DHEAS, and free testosterone were measured. Levels of androstenedione (A4), DHEA, 11-OHA4, and ADIOL were determined before (Steroid0) and 60 minutes after (Steroid60) acute ACTH-(1-24) stimulation. RESULT(S): Patients with NCAH had higher median basal levels of DHEAS and total and free testosterone than controls. Patients with NCAH had higher median A4(0), A460, DHEA(0), DHEA60, 11-OHA4(0), ADIOL0, and ADIOL60 levels but similar 11-OHA4(60) levels compared with controls. Among patients with NCAH, 30%, 54%, 15%, and 85% had 11-OHA4(0), ADIOL0, 11-OHA4(60), and ADIOL(60) levels, respectively, above the 95th percentile of controls. CONCLUSION(S): Overall, serum levels of 11-OHA4 did not appear to be a very sensitive marker of excessive adrenal androgen production, at least in patients with NCAH. Although ACTH-stimulated ADIOL levels were elevated in 85% of the patients studied, they did not appear to have any advantage over the measurement of A4 or DHEA levels.
Asunto(s)
Hiperplasia Suprarrenal Congénita/metabolismo , Andrógenos/biosíntesis , Androstenodiona/análogos & derivados , Adulto , Androstenodiona/sangre , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To prospectively establish the specificity, sensitivity, and positive predictive value (PPV) of a basal 17-hydroxyprogesterone (17-HP) level for the screening of 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) among hyperandrogenic women. DESIGN: Prospective observational trial. SETTING: Tertiary care academic medical centers. PATIENT(S): Eight healthy controls, 20 patients with NCAH, and 284 consecutively seen patients with hyperandrogenism. INTERVENTION(S): All controls and patients with NCAH, and select patients with hyperandrogenism, underwent acute ACTH (1-24) stimulation. MAIN OUTCOME MEASURE(S): Specificity was determined by measuring 17-HP every other day during one menstrual cycle in 8 healthy women with normal ovulation (107 samples). Sensitivity was determined by measuring 17-HP between 7 and 9 A.M. and 3 and 5 P.M. on the same day in 20 patients with genetically confirmed NCAH. The PPV was determined by prospectively measuring 17-HP in 284 consecutively seen hyperandrogenic women at their initial evaluation. The diagnosis of NCAH was established by a stimulated 17-HP level of >10 ng/mL. RESULT(S): Among controls, 17-HP levels of <2, <3, and <4 ng/mL all had a specificity of 100% when obtained in the follicular phase; when obtained in the luteal phase, they had specificities of 53%, 82%, and 82%, respectively. Among patients with NCAH, 17-HP levels of >2, >3, and >4 ng/mL had sensitivities of 100%, 90%, and 90%, respectively, for the detection of the disorder when obtained in the morning, and sensitivities of 95%, 90%, and 85%, respectively, when obtained in the afternoon. Among the 284 consecutively seen hyperandrogenic women, the PPVs of the first and second 17-HP levels were 7.3% and 19% for a cutoff level of >2 ng/mL, 13% and 43% for a cutoff level of >3 ng/mL, and 33% and 40% for a cutoff level of >4 ng/mL, respectively. CONCLUSION(S): A basal 17-HP level is a useful screening tool for NCAH. A cutoff level of 4 ng/mL has maximum specificity and PPV, with little loss in sensitivity if testing is performed in the morning and during the follicular phase. However, a lower cutoff level (e.g., 2 or 3 ng/mL) is preferable if testing is performed at odd hours of the day, as is common in many practices, and maximum sensitivity is desired.
Asunto(s)
17-alfa-Hidroxiprogesterona/metabolismo , Hiperplasia Suprarrenal Congénita/enzimología , Tamizaje Masivo/métodos , Glándulas Suprarrenales/enzimología , Metabolismo Basal , Estudios de Casos y Controles , Femenino , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To determine the prevalence of the polycystic ovary syndrome (PCOS) among women seeking electrology, clients presenting to nine electrology centers completed a questionnaire. STUDY DESIGN: Women with potential risk factors were referred to the University of Alabama at Birmingham. They underwent a detailed history and physical examination, including hirsutism scoring by a modified Ferriman-Gallwey (F-G) method. Serum was assayed for total testosterone, sex hormone binding globulin and dehydroepiandrosterone sulfate. RESULTS: Three hundred fifteen (40%) of 779 patients had potential risk factors for hyperandrogenism and were referred. Eighty-two (26%) completed their evaluation. Six were excluded secondary to prepubertal or menopausal status. Of the remaining 76 patients, 20% had F-G scores of 7 or 8, 13% had scores of 9 or 10, and 21% had scores > 10. Forty-nine (64%) patients reported irregular menstrual cycles. Sixty-four patients were not receiving hormonal therapy: 25 reported regular menstrual cycles, and 39 reported irregular cycles. Seventeen (68%) of the 25 had at least one abnormal androgen value, while 33 (85%) of the 39 women had at least one abnormal value (nonsignificant difference). Overall, PCOS was evident in 39 of the 76 women, or 12% of the 315 patients who were referred for further evaluation. CONCLUSION: Thirty-nine of the 315 referred patients (12%) fulfilled the diagnostic criteria for PCOS. However, they were not receiving medical care for this condition. In addition, this percentage is a conservative estimate in that 74% of the referred patients did not pursue a medical evaluation. Therefore, efforts to educate both electrologists and their clients of the possibility of underlying endocrine disorders and subsequent metabolic morbidity should be undertaken.
Asunto(s)
Hirsutismo/etiología , Hiperandrogenismo/diagnóstico , Síndrome del Ovario Poliquístico/epidemiología , Adulto , Estudios Transversales , Terapia por Estimulación Eléctrica , Femenino , Hirsutismo/terapia , Humanos , Hiperandrogenismo/complicaciones , Incidencia , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Factores de RiesgoRESUMEN
OBJECTIVE: Our goal was to prospectively evaluate the use of the free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for the detection of fetal Down syndrome and other aneuploidies. STUDY DESIGN: Women who had a second-trimester multiple-marker screening test (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and genetic amniocentesis from August 1996 to August 1998 were included. Serum was also analyzed for inhibin and the free beta-subunit of human chorionic gonadotropin. Detection and false-positive rates for 4 analyte combinations at 5 different screening risk cutoff points for Down syndrome were determined and compared. RESULTS: We evaluated 1256 patients, including 23 with aneuploidy (13 with Down syndrome, 10 others). The maternal age was 35.9 +/- 4.6 years (mean +/- SD). At the optimal risk cutoff point for Down syndrome detection (1:190; false-positive rate, 19%), the multiple-marker screening test plus inhibin was superior, detecting 85% of Down syndrome cases, in comparison with 69% when the multiple-marker screening test alone was used and 62% when the other 2 combinations were used. The multiple-marker screening test plus inhibin also detected 60% of the other aneuploidies. CONCLUSIONS: When evaluated prospectively in a high-risk population, the multiple-marker screening test plus inhibin was superior to the traditional multiple-marker screening test and 2 other analyte combinations, with a lower false-positive rate and increased detection of all aneuploidies in a high-risk population.
Asunto(s)
Aneuploidia , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Inhibinas/sangre , Diagnóstico Prenatal/métodos , Amniocentesis , Gonadotropina Coriónica/sangre , Dimerización , Síndrome de Down/diagnóstico , Estriol/sangre , Reacciones Falso Positivas , Femenino , Eliminación de Gen , Humanos , Embarazo , Estudios Prospectivos , Translocación Genética , Trisomía , alfa-Fetoproteínas/análisisRESUMEN
OBJECTIVE: We sought to determine the prevalence of 3beta-hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia among adult hyperandrogenic women with dehydroepiandrosterone sulfate excess. STUDY DESIGN: Thirty consecutive hyperandrogenic women with hirsutism, oligomenorrhea, or both and dehydroepiandrosterone sulfate levels of >8.5 micromol/L and 24 control subjects were studied. Basal sex hormone binding globulin, total and free testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, and basal and 60-minute corticotropin-stimulated 17-hydroxypregnenolone and dehydroepiandrosterone were measured, and the increment (change from basal to 60-minute value) was calculated. RESULTS: Twenty-six (87%) and 25 (83%) of the 30 hyperandrogenic patients studied had 60-minute dehydroepiandrosterone and change in 0- to 60-minute dehydroepiandrosterone levels greater than the mean + 2 SD of control subjects, respectively. Six (20%) and 6 (20%) of the 30 hyperandrogenic patients had 60-minute 17-hydroxypregnenolone and 0- to 60-minute change in 17-hydroxypregnenolone levels greater than the mean + 2 SD of control subjects, respectively. However, none of the subjects had either 60-minute 17-hydroxypregnenolone levels or 60-minute dehydroepiandrosterone levels or both associated with the diagnosis of genetically proved 3beta-hydroxysteroid dehydrogenase deficiency (>5-fold of the control mean value). CONCLUSION: 3beta-Hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia is rare even among adult hyperandrogenic patients with adrenal androgen excess.
Asunto(s)
3-Hidroxiesteroide Deshidrogenasas/deficiencia , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperandrogenismo/complicaciones , 17-alfa-Hidroxiprogesterona/sangre , Adolescente , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/enzimología , Hormona Adrenocorticotrópica , Adulto , Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Hiperandrogenismo/sangre , Hiperandrogenismo/enzimología , Cinética , Testosterona/sangreRESUMEN
OBJECTIVE: To determine whether DHEAS levels in hyperandrogenic (HA) women retain the normal age-related decrease. DESIGN: Prospective study. SETTING: Academic tertiary care medical center. PATIENT(S): One hundred forty-five HA patients with hirsutism and/or oligo-ovulation and 53 healthy women. INTERVENTION(S): Blood samples were obtained on days 3-8 of the menstrual cycle or after an IM progesterone-induced withdrawal bleed. MAIN OUTCOME MEASURE(S): Serum samples were assayed for progesterone, total testosterone, sex hormone-binding globulin, free testosterone, and DHEAS. RESULT(S): Controls and HA patients were similar in body mass index and age. A negative correlation between DHEAS levels and age, but not body mass index, was found among controls. In HA patients. DHEAS levels decreased with age. Dehydroepiandrosterone sulfate levels correlated with the hirsutism score in HA patients. When HA patients were subdivided into those with low, middle, and high DHEAS levels, those with low DHEAS levels were older and weighed more than those with high DHEAS levels. CONCLUSION(S): The negative association between DHEAS levels and age is preserved in HA women. Hyperandrogenic patients with high DHEAS levels are younger, thinner, and more hirsute than those with lower DHEAS levels. These findings suggest that the diagnosis of adrenal androgen excess in HA patients may require the use of age-adjusted normative values.
Asunto(s)
Envejecimiento , Índice de Masa Corporal , Sulfato de Deshidroepiandrosterona/sangre , Hiperandrogenismo/sangre , Adulto , Constitución Corporal , Femenino , Hirsutismo/sangre , Humanos , Síndrome del Ovario Poliquístico/sangre , Progesterona/sangre , Estudios Prospectivos , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangreRESUMEN
Sex steroid levels and steroid metabolism were investigated in relation to early gonadal development in a mixed sex population of the tilapia Oreochromis niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts. Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and metabolites were identified by thin-layer chromatography coupled with radioisotope image analysis. Histology revealed the presence of gonadal structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other individuals exhibiting undifferentiated gonads containing germinal cells, presumably eventual testes. Androgen levels were initially high in eggs then decreased severalfold prior to the emergence of gonads. A transient increase in the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or undetectable except for a transient increase (43 dpf) after ovaries were present. Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally increased throughout development. Metabolites were generally similar, consisting of T predominantly as well as 5beta-reduced androgen derivatives and 11-oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids were not formed. Two types of steroid metabolic profiles occurred at 50 dpf. These results demonstrate that changes in the steroidogenic profile occur during early transitions of gonadal development. Notably, (1) steroid biosynthetic capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs after ovarian development has begun, and (3) bimodality of levels of T and differential steroid metabolism later in development may reflect the onset of sexual divergence.
Asunto(s)
Desarrollo Embrionario , Ovario/metabolismo , Esteroides/metabolismo , Testículo/metabolismo , Tilapia/metabolismo , Androstenodiona/metabolismo , Animales , Estradiol/metabolismo , Femenino , Masculino , Ovario/embriología , Radioinmunoensayo , Testículo/embriología , Testosterona/análogos & derivados , Testosterona/metabolismo , Tilapia/embriologíaRESUMEN
Adrenal androgen (AA) excess, primarily in the form of dehydroepiandrosterone sulfate (DHEAS), affects over 50% of women with the polycystic ovary syndrome (PCOS). Nonetheless, it is unclear what role AA excess plays in the PCOS-associated oligo-ovulation. We have hypothesized that AAs are important in the maintenance of the ovulatory dysfunction of women with PCOS and AA excess, which can be improved by glucocorticoid suppression. To test our hypothesis we prospectively studied 36 unselected women, ages 18-40 yr, with PCOS; i.e. oligomenorrhea (cycles > 35 days in length), and clinical/ biochemical evidence of hyperandrogenism (i.e. hirsutism and/or hyperandrogenemia), after the exclusion of related disorders. After informed consent, all patients underwent an acute ACTH-(1-24) stimulation test, measuring androstenedione, dehydroepiandrosterone (DHEA) and cortisol (F), and were then treated with dexamethasone 0.5 mg/day for four cycles. Ovulatory function was assessed before and during treatment using a basal body temperature calendar and day 22-24 progesterone (P4) levels. If patients were anovulatory (P4 < 4 ng/mL), a withdrawal bleed was induced by the administration of 100 mg P4 in oil i.m. Before and during treatment the levels of total and free testosterone (T), sex hormone-binding globulin, androstenedione, DHEA, DHEAS, cortisol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were monitored. With therapy, all patients demonstrated a significant decrease in all androgens (-40-60%), a 24% increase in sex hormone-binding globulin, and no change in LH/FSH. Mean body weight increased by over 4 kg (4.4%) during treatment. Of the 138 cycles monitored, 78% remained anovulatory. Twenty-five percent, 17%, 14%, and 20% of the first, second, third, and fourth treatment cycles, were ovulatory, respectively (P = 0.381). Of the 36 patients studied, 18 (50%) did not demonstrate a single ovulatory cycle (i.e. a day 22-24 P4 level > 4 ng/mL); and of the remaining, 10 (28%) had only one, five (14%) had two, and three (8%) had three ovulatory cycles. There were no significant differences either in physical features, basal hormones, adrenal response to ACTH stimulation, or hormonal levels at the end of treatment, between those women ovulating and those not. Finally, there were no differences in ovulatory response to dexamethasone therapy between women with (n = 14) and without (n = 22) DHEAS excess (i.e. DHEAS > 2750 ng/mL). In conclusion, the data from this prospective study do not suggest that continuous dexamethasone suppression results in consistent ovulation in any PCOS patient, regardless of basal DHEAS levels. Furthermore, this treatment is associated with significant side-effects, notably weight gain. Finally, these data suggest that, while AA may be an important risk factor for PCOS, once the syndrome is established, they play a limited role in the associated ovulatory dysfunction.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Sulfato de Deshidroepiandrosterona/sangre , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Ovulación/fisiología , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/fisiopatología , Adolescente , Adulto , Andrógenos/sangre , Femenino , Predicción , Humanos , Ovulación/efectos de los fármacos , Síndrome del Ovario Poliquístico/sangre , Estudios ProspectivosRESUMEN
OBJECTIVE: To determine if a polymorphism of the dopamine D3 receptor gene (2 allele), which has been reported previously to be associated with polycystic ovary syndrome (PCOS) in a population of United States Hispanic women, is associated with the disorder in the southeastern United States. DESIGN: Prospective case-control study. SETTING: University reproductive endocrinology laboratory and outpatient clinic. PATIENT(S): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 152) and healthy controls (n = 96). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patient and control dopamine D3 receptor genotypes, with the 1 allele representing the wild type and the 2 allele denoting a highly prevalent polymorphism. RESULT(S): No difference was noted in the distribution of the three dopamine D3 receptor genotypes (i.e., 1:1, 1:2, and 2:2) among PCOS patients as compared with controls. Furthermore, in contrast to a previous report, the 2:2 genotype was not more prevalent among PCOS patients than among controls. CONCLUSION(S): Our population of non-Hispanic white women from the southeastern United States did not demonstrate an association between a dopamine D3 receptor polymorphism and PCOS.
Asunto(s)
Síndrome del Ovario Poliquístico/genética , Receptores de Dopamina D2/genética , Población Blanca/genética , Adulto , Alelos , Estudios de Casos y Controles , ADN/análisis , Femenino , Genotipo , Hispánicos o Latinos/genética , Humanos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/epidemiología , Polimorfismo Genético , Receptores de Dopamina D2/sangre , Receptores de Dopamina D3 , Sudeste de Estados Unidos/epidemiologíaRESUMEN
Androgen excess affects between 2% and 10% of women. While the majority of these patients suffer from polycystic ovary syndrome, a few present with an androgen-secreting neoplasm. An elevated circulating total testosterone level and dehydroepiandiosterone sulfate (DHEAS) level have been proposed as screening methods for detecting ovarian and adrenal androgen-secreting neoplasms, respectively. To determine the predictive value of these tests for androgen-secreting tumors in a population of consecutive hyperandrogenic patients, we studied 478 consecutive untreated hyperandrogenic patients presenting over a ten-year period (1987-97). All had at least two of the following features: (1) oligomenorrhea (i.e. cycles > 35 days or < 8 cycles/year), (2) hyperandrogenemia (i.e. a total or free testosterone, or DHEAS > 95th percentile of controls), or (3) hirsutism (i.e. a modified Ferriman-Gallwey score > or = 6). None of these patients had a prior diagnosis of an androgen-secreting neoplasm. Basal levels of testosterone and DHEAS were determined in all patients, with transvaginal sonography and an adrenal computed tomography scan in select individuals. Of the 478 patients included, 65% had hirsutism and oligomenorrhea; 20% had hyperandrogenic oligomenorrhea; and 15% had hirsutism and hyperandrogenemia, without overt oligomenorrhea. Overall, 11 (2.3%) patients had a total testosterone > 8.7 nmol/l (250 ng/dl), of which one actually had an androgen-secreting neoplasm (i.e. true-positive). This postmenopausal patient presented with rapidly progressive virilization, and demonstrated an ovarian hilar cell tumor at surgery. The calculated sensitivity of an elevated testosterone level (> 8.67 nmol/l) for a neoplasm was 100% (1/1), the specificity was 98% (467/477), and the negative predictive value was 100% (467/467), but the positive predictive value was only 9% (1/11). Ten subjects had DHEAS levels > 16.3 mumol/l (6000 ng/ml), and none was diagnosed with an adrenocortical tumor. Although the sensitivity and positive predictive value of a high DHEAS for a neoplasm could not be calculated due to the absence of a test case, the specificity was 98% (468/478) and the negative predictive value was 100% (468/468). These data suggest that the measurement of testosterone and DHEAS is not a cost-effective method of screening for these tumors, due to the low frequency of the disorder and the fact that clinical evaluation alone is often sufficient screening.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/metabolismo , Andrógenos/metabolismo , Sulfato de Deshidroepiandrosterona/sangre , Hiperandrogenismo/etiología , Neoplasias Ováricas/metabolismo , Testosterona/sangre , Neoplasias de la Corteza Suprarrenal/complicaciones , Femenino , Hirsutismo/etiología , Humanos , Oligomenorrea/etiología , Neoplasias Ováricas/complicaciones , Posmenopausia , Virilismo/etiologíaRESUMEN
OBJECTIVE: Our purpose was to determine whether the combination of maternal serum alpha-fetoprotein, free human chorionic gonadotropin-beta, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. STUDY DESIGN: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 +/- 5.6 years). Alpha-fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-beta and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. RESULTS: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of alpha-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner's syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). CONCLUSIONS: The combination of maternal serum alpha-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination.