Joaquín Herrera

Obesity differentially affects serum levels of androstenedione and testosterone in polycystic ovary syndrome

OBJECTIVE To assess androstenedione (A) and T levels in obese and nonobese patients with polycystic ovary syndrome (PCOS) after GnRH and oral glucose tolerance tests (OGTT). DESIGN Cross sectional study. SETTING Clinical research center. PATIENT(S) Thirty patients with PCOS, of whom 15 were obese and 15 were nonobese, and 7 women without PCOS were included in the study. INTERVENTION(S) The GnRH test and OGTT were performed in all subjects. MAIN OUTCOME MEASURE(S) Basal and stimulated levels of LH, FSH, insulin, A, and total T were measured. Areas under the curve (AUCs) and AUC change after stimulation for these hormones were calculated. RESULT(S) The basal T levels were significantly higher in obese than in nonobese patients with PCOS. In contrast, the basal levels of A were similar in obese and nonobese patients with PCOS. The T(AUC) after GnRH was significantly greater in obese than in nonobese patients with PCOS but was not significantly different after OGTT. The A(AUC) after GnRH and OGTT was significantly greater in nonobese than in obese patients with PCOS. However, there were no significant differences in T(AUC) and A(AUC) changes after GnRH and OGTT. CONCLUSION(S) A different pattern in the levels of T and A with respect to obesity in PCOS was observed, suggesting a shift in ovarian enzymatic function.

Normal ovarian function in a mild form of late-onset 3β-hydroxysteroid dehydrogenase deficiency*

Late-onset 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency was diagnosed in a 30-year-old woman with hirsutism and normal menstrual cycles. No genital abnormalities were present. Elevated basal serum levels of delta 5-3 beta-hydroxysteroids were demonstrated. Serum pregnenolone (P5) was 3.0 ng/ml, and dehydroepiandrosterone sulphate (DHEA-S) 3245 ng/ml. Basal serum levels of delta 4 steroids were low or within normal limits. Serum progesterone (P) was 0.5 ng/ml, 17 alpha-hydroxyprogesterone (17-OHP) 0.2 ng/ml, androstenedione (delta 4A) 0.4 ng/ml, and testosterone (T) 0.1 ng/ml. All delta 5/delta 4 steroid ratios were elevated. Dexamethasone (DEX) administration normalized the elevated levels of delta 5-3 beta-hydroxysteroids, whereas delta 4-3-ketometabolites exhibited only minor modifications. The DHEA-S/delta 4A ratio increased more than five times over the basal ratio, and P5/P and 17 alpha-hydroxypregnenolone (17-OHP5)/17-OHP ratios did not increase after adrenocorticotrophic hormone ACTH stimulation. Studies of basal ovarian function revealed 17 beta-estradiol (E2) and gonadotropins within normal limits according to the menstrual cycle. In the follicular phase, follicle-stimulating hormone (FSH) was 101.3 ng/ml, luteinizing hormone (LH) 46.0 ng/ml, and E2 49.7 pg/ml; in the luteal phase, FSH was 180.0 ng/ml, LH 69.3 ng/ml, and E2 50.1 pg/ml. The presence of ovulatory cycles was documented on the basis of the biphasic pattern of the basal body temperature cycles and the increment in P levels. This case demonstrates the existence of normal ovulatory function in a woman with late-onset of a mild form of HSD.

Determination of the steroidogenic capacity in premature ovarian failure

OBJECTIVE To determine the secretion of precursors, intermediate and final products of androgen biosynthesis in women with premature ovarian failure (POF). PATIENTS Seven patients 20 to 34 years of age with idiopathic POF and a control group of six women 27 to 29 years of age with normal ovarian function studied during the early follicular phase were included. DESIGN, INTERVENTIONS: In all patients an adrenal stimulation test was performed as follows: a short dexamethasone (DEX) inhibition was carried out the night before the corticotropin (ACTH, 0.25 mg, Cortrosyn; Organon, Orangeburg, NY) stimulation test, obtaining blood samples in basal conditions, post-DEX inhibition as well as at 60, 120, and 180 minutes after the ACTH bolus. MAIN OUTCOME MEASURES Using specific RIA serum concentrations of delta 5 precursors (pregnenolone, 17-hydroxypregnenolone, DHEA), delta 4 intermediates (P, 17-hydroxyprogesterone, androstenedione) and the final products T and cortisol (F) were measured. RESULTS Adrenal inhibition and stimulation responses in both groups of patients showed no differences for delta 5 precursors and F. On the other hand, delta 4 intermediates and androgens exhibited significant differences at the level of response to ACTH stimulation. Patients with POF had significantly lower values than those of control group. CONCLUSION An important decrement in the steroidogenesis was noticed in POF, particularly in androgen synthesis, revealing the selective participation of the adrenal gland in steroid production.

Subcellular metabolic pools in the rat adrenal gland. In vivo effect of acute stimulation with ACTH on steroid biosynthesis.

Abstract To determine the metabolic pool changes during acute ACTH infusion, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, corticosterone and cortisol were measured by RIA in subcellular fractions from rat adrenal glands. The in vivo effect of ACTH on steroid biosynthesis was deduced from correlations between subcellular fraction measurements and serum concentrations values, permitting a dynamic interpretation of results. Twenty six Sprague-Dawley male rats, received 0.1 I.U./g of body weight of ACTH I.P. while eighteen (control group) received isotonic saline solution. Rats in both groups were decapitated immediately and at 5, 10 and 20 min after injection. Results showed the highest serum concentrations of corticosterone at time zero. Pregnenolone and corticosterone concentrations were highest in the mitochondrial fraction while progesterone was in the microsomal fraction. Exogenous ACTH depleted-pregnenolone and progesterone pools increasing the corticosterone pool as well as its serum concentration, with minor modifications in other steroids. Its maximal effect occurred at 10 min. In contrast with previous reports, it was found that 17-hydroxylated compounds such as cortisol, revealing 17-hydroxylase enzyme activity. It is concluded that ACTH not only stimulates pregnenolone synthesis but also increases the enzymatic activity of other systems which use this compound as a substrate to produce corticosterone.

Disability-adjusted life-years (DALYs) for diabetes in Mexico in 2005: a cross-sectional burden of disease analysis

Abstract Background Diabetes is one of the leading causes of morbidity and mortality in Mexico and its prevalence has been rising since the end of the last century. The aim of this study was to estimate, for 2005, the share of burden due to this disease in the Instituto Mexicano del Seguro Social—the major social security institution in Mexico, which covers nearly half of Mexicos population. Methods Disability-adjusted life-years (DALYs) were calculated by the sum of the estimated years of life lost (YLLs) and years lived with disability (YLDs) due to diabetes. The International Statistical Classification of Disease and Related Health Problems 10th Revision was used, and we included the E10–E14 codes related to diabetes mellitus. YLLs were calculated from age–sex–time-specific estimates of mortality by diabetes. YLDs were calculated by age and sex, and prevalence of diabetes and its disabling sequelae such as retinopathy, amputation, diabetic foot, and neuropathy. Findings In 2005, diabetes contributed 787 397 DALYs, 9·21% (95% CI 9·19–9·23) of total DALYs in Mexico, an increase from 7·31% (7·28–7·33) estimated in 1995. 5·83% (95% CI 5·79–5·89) of DALYs due to diabetes were attributed to retinopathy, 2·62% (2·58–2·65) to amputation, and 0·94% (0·92–0·96) to diabetic foot and neuropathy. While in adults aged between 25 and 44 years of age 64·29% (95% CI 64·00–64·60) of DALYs were due to YLDs, this proportion was 18·70% (18·50–18·90) in adults aged 45–59 years and only 6·47% (6·39–6·54) in those aged 60 years and older. 55·52% (95% CI 55·40–55·60) of the population affected with DALYs due to diabetes were female. Interpretation In recent years, diabetes has been challenging the Mexican health-care system due to its high mortality rate and its high costs of care. In spite of the burden due to mortality, there is also a high burden due to YLDs, mainly among the younger age groups. Some neglected microvascular complications of diabetes, such as retinopathy, neuropathy, and diabetic foot, have contributed considerably to DALYs in Mexico. Funding Mexican Social Security Institute (Grant No. 2005-785-154).

Modulation of luteinizing hormone secretion by estrogens in patients with Reifenstein’s syndrome*

The role of estrogens on gonadotropin secretion was assessed in two siblings with incomplete virilization syndrome type I due to partial androgen insensitivity (Reinfensteins syndrome). Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured before and after 100 micrograms LH-releasing hormone (RH) intravenous (IV) stimulation, as well as during long-term clomiphene citrate (CC) administration. Serum testosterone (T) and estrogens were determined before and during daily administration of human chronic gonadotropin (hCG) and also during the CC treatment. Basal levels of LH were elevated in both patients: 12.5 +/- 1.1 mIU in patient A and 19.8 +/- 1.8 mIU/ml in patient B. Conversely, FSH levels were within normal limits. Administration of LH-RH in both subjects induced a rise in LH levels, while FSH concentration showed no increase. The CC administration resulted in a significant (P less than 0.005) increment in serum LH levels without changes in FSH concentration. An important increase of serum T and estradiol (E2) levels was noted during CC administration; thus, in patient A those levels augmented from 20 to 48 ng/ml for T and from 78 to 220 pg/ml for E2; and patient B showed an increment from 20 to 35 ng/ml for T, and from 55 to 180 pg/ml for E2. The daily administration of hCG was followed by an increment in both T and E2 levels, which was of lesser degree for estrone concentration. These results suggest that endogenous estrogens, particularly E2, modulate LH secretion in patients with partial androgen insensitivity; however, it appears that estrogens had no physiologic effect on FSH secretion.