[Treatment of hirsutism with spironolactone and with spironolactone plus dexamethasone]. / Tratamiento del hirsutismo con espironolactona y con espironolactona más dexametasona.

BACKGROUND: Spironolactone has an anti androgenic effect, inhibiting the binding of androgens to their receptor. This antagonistic effect is the basis for the use of spironolactone in the treatment of hirsutism. AIM: To study the effectiveness and safety of spironolactone in the treatment of hirsute women and of the association of spironolactone plus dexamethasone in the treatment of hirsutism with glucocorticoid sensitive hyperandrogenism. PATIENTS AND METHOD: Sixteen women (group 1) with peripheral hirsutism (defined as those with normal androgens levels, normal menstrual cycles and ovulation) and 24 women (group 2) with glucocorticoid sensitive hyperandrogenic hirsutism were studied. Group 1 was treated with spironolactone 50 mg hid and group 2 with same spironolactone dose plus dexamethasone 0.5 mg at 23 h during one month and 0.25 mg thereafter. Patients were followed during one year. RESULTS: After one year of treatment, a 54% reduction in Moncada hirsutism escore was observed in group 1 and 52% reduction in group 2. Observed secondary effects of spironolactone were increases in diuresis, fatigability, acne aggravation and seborrhea in two patients. Two additional patients had spotting. No secondary effect attributable to glucocorticoid use were observed. CONCLUSIONS: Spironolactone is effective and safe in the treatment of hirsutism. Androgenic supression did no increases its effectiveness, underscoring the peripheral anti androgenic activity os spironolactone.

Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina.

We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies.

[Causes of male infertility. The contribution of the endocrine factor]. / Factores causales de infertilidad masculina. Contribución del factor endocrino.

BACKGROUND: Male infertility is responsible for 35% of infertile couples. AIM: To investigate the causes of male infertility and the relative importance of endocrine factors. PATIENTS AND METHODS: Patients referred to an andrology clinic due to an abnormal spermiogram were studied. A testicular examination, spermiogram and determination of FSH, LH, testosterone and prolactin were done to all. Testicular biopsy was done to patients with severe oligospermia or azoospermia. Causes of infertility were defined and classified as pretesticular, testicular, posttesticular or unclassified. RESULTS: Two hundred fifty seven males were studied. In 3.5% of them, the cause of infertility was defined as pretesticular (that included hypothalamic and pituitary endocrine causes), in 66.9% it was classified as testicular, in 15.6% as posttesticular and in 14%, as unclassified. Thirty percent of infertility cases were idiopathic, 17.9% were associated to varicocele, 12.8% were associated to cryptorchidism, 8.9% to Klinefelter syndrome and 6.6% to exposure to toxic substances. In 50% of patients with cryptorchidism, this abnormality was found during the specialized andrological examination and referrals for surgical correction were made late. Two thirds of patients with Klinefelter syndrome were hypoandrogenic. CONCLUSIONS: Causes for male infertility should be investigated and diagnosed accurately. Primary hypoandrogenic testicular failures must be treated with hormone replacement therapy.

Environmental contaminants and body fat distribution.

The effect of body mass index (BMI) and waist:hip ratio (WHR) on plasma levels of organochlorines [i.e., 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)] was investigated in a sample of black and white women drawn from a population-based study in North Carolina. Organochlorine levels were determined in plasma samples from 99 women selected on the basis of race (black versus white) and quartile of the WHR (1st versus 4th). Of a panel of 20 organochlorine compounds tested, only DDE was detectable in most study subjects. Measurements of height, weight, and waist and hip circumferences were taken during an in-person interview. Information was elicited regarding dietary, residential, and breast-feeding histories. Results of multiple regression analyses indicate that black women had significantly higher plasma levels of DDE than white women. These levels were independent of BMI and WHR. BMI but not WHR was also found to be an independent predictor of DDE plasma level. These results suggest that black/white differences should be considered in studies that explore the relationship between environmental contaminants and various disease outcomes, such as breast cancer risk. In addition, BMI may affect circulating levels of contaminants and should also be considered a potentially important modifying factor for exposure to lipophilic substances.

[Has oligomenorrhea a pathological meaning? The importance of this symptom in internal medicine]. / Tiene la oligomenorrea un significado patológico? Importancia de este síntoma en medicina interna.

BACKGROUND: Oligomenorrhea, defined as a menstrual cycle lasting 36 to 90 days, can be a normal condition in the first years after the menarche. When it persists or appears after a period of normal menstrual cycles, an underlying illness must be sought. AIM: To assess ovulation and causes of anovulatory cycles in women with oligomenorrhea, compared with causes of secondary amenorrhea. PATIENTS AND METHODS: One hundred one women of less the 35 years old, presenting with oligomenorrhea persisting 5 years after menarche or lasting more than two years after a period of normal menstrual cycles, were studied. Ovulation was studied measuring serial plasma progesterone during normal or induced (with intramuscular progesterone) menstrual cycles. RESULTS: Eighty nine percent of women had anovulatory oligomenorrhea. The main causes were polycystic ovarian disease in 51% and hypothalamic dysfunction in 31%. Thirty percent of women with secondary amenorrhea had polycystic ovarian disease and 14% had hyperprolactinemia. Women older than 20 years old or with more than 10 years of gynecological age had a higher frequency of polycystic ovarian disease and a lower prevalence of hypothalamic dysfunction. CONCLUSIONS: There is a high frequency of anovulatory oligomenorrheas. Therefore, this symptom deserves a thorough endocrinological assessment to uncover underlying diseases. Special attention must be paid to polycystic ovary syndrome, due to its importance in internal medicine as a risk factor for myocardial infarction, high blood pressure, and type 2 diabetes mellitus.

Some dietary predictors of plasma organochlorine concentrations in an elderly German population.

Associations between reported consumption of animal products and chlorinated hydrocarbon concentrations were examined in 297 elderly people who lived in Germany. Consumption of beef and lamb was correlated positively with hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), total polychlorinated biphenyls (PCBs), and total dichloro-diphenyl-trichloroethane (DDT) (r = .13-.19, p < .05). Consumption of saltwater fish was correlated positively with alpha-HCH, dieldrin, and PCBs (r = .12-.26, p < .05). Other univariate predictors were body mass index, plasma cholesterol, pork consumption, poultry consumption, and age. Multivariate linear models of predictors of each chlorinated species were constructed, and some form of meat was used as the main predictor; the sum of all meats (exclusive of fish) was the best predictor of dieldrin and In(alpha-HCH) concentrations. Beef and lamb consumption was a positive predictor of HCB, heptachlor epoxide, total DDT, and beta-HCH. Saltwater fish was the major dietary predictor of PCBs.

Correlations among human blood levels of specific PCB congeners and implications for epidemiologic studies.

Specific congeners of PCBs may differ with respect to their human health risks. For epidemiologic studies, however, measuring levels of specific congeners--as compared with estimating the concentration of total PCBs present, may be of limited value if levels of specific congeners are highly correlated. We examined the correlations among levels of specific congeners in three groups: controls from a case-control study of breast cancer in North Carolina and two groups from Wisconsin with exposure to fish from contaminated waters. Levels of specific congeners were, in general, highly correlated (Pearson r > 0.80). However, the level of congener 180, a heptachlorobiphenyl, tended to be less correlated with levels of lower-chlorinated biphenyls. Among the implications of these findings are that measurement of a select group of congeners may yield essentially the same information as measurement of a large panel, and may be more cost efficient.

Obesity as a protective factor for postmenopausal osteoporosis.

BACKGROUND: Obesity is considered a protective factor for osteoporosis improving bone mass and maintaining higher levels of estrogen during menopause. OBJECTIVE: To determine the association of obesity with bone mineral density (BMD), and its relationship with sex hormone levels. DESIGN: A case-control study in Caucasian obese and non obese postmenopausal women. SUBJECTS: 113 obese and 50 non-obese postmenopausal women. MEASUREMENTS: BMD (dual-photon X-ray absorptiometry) at cervical femur. Ward's triangle, proximal radius and lumbar spine. Plasma levels of glucose, insulin, total estrogen, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHA-S) and testosterone. RESULTS: Mean BMD at femoral sites were significantly higher in obese women (femoral neck: 0.849 +/- 0.124 g/cm2 vs 0.753 +/- 0.095 g/cm2, P < 0.001; Ward's triangle: 0.634 +/- 0.134 g/cm2 vs. 0.553 +/- 0.100 g/cm2, P < 0.001). Mean BMD at lumbar spine was 0.906 +/- 0.138 g/cm2 in obese women and 0.849 +/- 0.137 g/cm2 in non obese, P < 0.017. A decreased risk of osteopenia in femoral neck (Age adjusted OR = 0.36, 95%CI 0.17-0.75) and in lumbar spine (Age adjusted OR = 0.43, 95%CI 0.20-0.91) in obese women was observed. Although total estrogen were similar in both groups, in obese women, SHBG was lower (68.6 +/- 26.84 nmol/l vs. 85.1 +/- 31.18 nmol/l, P < 0.001), and postglucose load insulin levels were higher, than in non obese (77.2 +/- 50.4 Ul/ml vs. 49.4 +/- 24.1 Ul/ml, P < 0.0005). CONCLUSION: The findings confirm a higher BMD in obese women and suggest that obesity exerts protection due to a decreased SHBG thus increasing free sex steroids. Besides, hyperinsulinemia may produce a decline in the production of IGFBG-1, leading to an increase of IGF-1, that may stimulate the proliferation of osteoblasts.

Effects of abstinence on sex hormone profile in alcoholic patients without liver failure.

Excessive ethanol ingestion induces hypoandrogenism in male subjects. To confirm its presence and to study its relationship with the degree of liver damage and alcohol abstinence, plasma sex hormones were measured in alcoholic patients without liver failure, after two different abstinence periods. Patients were 30 male chronic alcoholics admitted to the Alcoholism Ward for treatment of their addiction. On admission, we measured: testosterone (T), estradiol (E), follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone binding globulin (SHBG). A liver biopsy was also performed. These measurements were repeated at discharge and were also done in 15 normal volunteers. On admission (mean abstinence 1.9 +/- 1.7 days) total T was similar to controls, FSH was lower (p < 0.02) and high levels of SHBG were found (3.5 fold increase, as compared to controls). Histologically, 9 patients had normal liver; 14 had moderate alterations and 7 showed marked alterations. Hormonal values were not different in these 3 groups. At discharge, 11.1 +/- 4.7 days after admission, T, E and FSH did not show significant changes but LH decreased (8.2 +/- 5.2 mIU/ml vs 12.9 +/- 4.1, p < 0.001); SHBG also decreased (65.4 +/- 21.6 nmol/l vs 117.2 +/- 33.3, p < 0.001) to values that still were twice those of controls. It is concluded that alcoholic patients without clinical signs of liver failure have normal plasma testosterone levels, irrespective of their histologic liver alterations and high plasma SHBG levels that decreased significantly after a short abstinence. The concomitant LH decrease suggests that hypoandrogenism is likely in these patients. Fast changes in SHBG levels rise the possibility that this protein is candidate marker of alcoholism.

[Functional adrenal hyperandrogenism: changing perspectives during its historical evolution]. / Hiperandrogenismo suprarrenal funcional: perspectivas cambiantes en su evolución histórica.

The approach to adrenal hyperandrogenism, due to genetical or non-genetical enzymatic alterations, has changed dramatically during the last 50 years. To allow a better understanding of the subject, we focused it from a historical perspective, defining four stages analyzed in detail. Now there is consent on the existence of a functional adrenal hyperandrogenism, which has an important role in acne, hirsutism and menstrual disturbances.

Studying environmental influences and breast cancer risk: suggestions for an integrated population-based approach.

Increased attention has focused in recent years on environmental exposures which may elevate risk of human breast cancer. Following a brief introduction to the topic, we present a summary of recent evidence regarding the role of chlorinated hydrocarbons (e.g. pesticides), occupational exposures (e.g. electromagnetic fields), dietary factors, and other hydrocarbons (e.g. tobacco). Next, we present suggestions for additional measurements which may help to clarify the contribution of environmental factors, including individual and ecologic level exposure histories, polymorphisms in carcinogen-metabolizing enzymes, and interactions among environmental exposures, breast tumor characteristics, and other risk factors for breast cancer. Finally, we discuss how a population-based approach may be used to integrate these sources of information and could provide new clues regarding the role of environmental influences in breast cancer.

[Prolonged remission of female hyperandrogenism after discontinuing glucocorticoid therapy]. / Remisión prolongada del hiperandrogenismo femenino después de suspender la terapia con glucocorticoides.

Adrenal androgen hypersecretion either produced by genetic defects or reticular disfunction, is reduced by exogenous glucocorticoid administration and, as with any suppression therapy, it should relapse when the therapy is discontinued. However, prolonged remissions of adrenal androgen hypersecretion after discontinuing glucocorticoids have been described. We report 15 patients with adrenal hyperandrogenism and elevated levels of dehydroepiandrosterone sulfate that received treatment with dexamethasone. After one month of treatment with dexamethasone 0.5 mg/day, dehydroepiandrosterone sulfate levels returned to normal and remained so during a mean of 19 months receiving dexamethasone 0.25 mg/day. One year after discontinuing therapy, hormone levels continued within normal range in all patients. It is concluded that a long remission period of adrenal hyperandrogenism was achieves after discontinuing glucocorticoid therapy.

The biological speciation and toxicokinetics of aluminum.

This review discusses recent literature on the chemical and physiological factors that influence the absorption, distribution, and excretion of aluminum in mammals, with particular regard to gastrointestinal absorption and speciation in plasma. Humans encounter aluminum, a ubiquitous yet highly insoluble element in most forms, in foods, drinking water, and pharmaceuticals. Exposure also occurs by inhalation of dust and aerosols, particularly in occupational settings. Absorption from the gut depends largely on pH and the presence of complexing ligands, particularly carboxylic acids, with which the metal can form absorbable neutral aluminum species. Uremic animals and humans experience higher than normal body burdens of aluminum despite increased urinary clearance of the metal. In plasma, 80-90% of aluminum binds to transferrin, an iron-transport protein for which receptors exist in many tissue. The remaining fraction of plasma aluminum takes the form of small-molecule hydroxy species and small complexes with carboxylic acids, phosphate, and, to a much lesser degree, amino acids. Most of these species have not been observed in vivo but are predicted from equilibrium models derived from potentiometric methods and NMR investigations. These models predict that the major small-molecule aluminum species under plasma conditions are charged and hence unavailable for uptake into tissues.

[Therapeutic usefulness of antiandrogens]. / Utilidad terapeutica de los antiandrogenos.

Antiandrogens are substances that block androgen receptors. The antiandrogenic action of some of these medications, as H2 blockers and some diuretics, was discovered as a collateral effect. They are used for the treatment of acne, hirsutism and seborrhea in women; they are also used in precocious puberty and sexual hyperexcitability states. The clinical usefulness of these drugs is unquestionable, but their prescription requires a through knowledge of their endocrinological effects.

[Amenorrhea, insulin resistance and acanthosis nigricans. A hyperandrogenic and a normoandrogenic clinical forms]. / Amenorrea, resistencia insulínica y acantosis nigricans. Una forma clínica hiperandrogenica y otra normoandrogenica.

Two cases of HAIR-AN syndrome (hyperandrogenism, insulin resistance and acanthosis nigricans) are presented. The first case corresponds to a female with a systemic lupus erythematosus and acanthosis nigricans in which an insulin resistance was documented; the patient was in amenorrhea with severe hypoestrogenism, although she did not have clinical signs of hyperandrogenism and serum androgen levels were normal. This case corresponds to a HAIR-AN syndrome associated to autoimmune diseases or type A of Kahn. The second case is a young female with clinical signs of hyperandrogenism associated to high testosterone levels; she had acanthosis nigricans and fasting and postprandial hyperinsulinemia. Probably, this case corresponds to a type A or C HAIR-AN syndrome in which there is a decrease in the number of insulin receptors or a post receptor defect in insulin action.

[The usefulness and importance of functional progesterone and estrogen tests in the study of amenorrheas]. / Utilidad e importancia de las pruebas funcionales de progesterona y estrógenos en el estudio de las amenorreas.

One hundred and eighty-two patients who complained of amenorrhea were tested with progesterone and oestrogen. The results are correlated with the diagnosis of the causes. The etiology is related with hypothalamic, hypophysiary, ovarian and/or uterine origins and dysfunction.

[Diffuse hyperthyroid goiter treated with I131, papillary carcinoma occurring after iodine radioisotope treatment, and thyroxine malabsorption. A clinical case]. / Bocio difuso hipertiroídeo, tratado con I131, cancer papilar de aparición post radioyodo y malabsorción de tiroxina. Caso clínico.

A 50 year-old male with diffuse hyperthyroid goiter treated with I131 who develops a papillary carcinoma is presented. After thyroid resection, substitution therapy with thyroid hormone (levothyroxine) was started, and a selective malabsorption for this hormone was verified.