• Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 ug/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX) Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH) Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 00001 except for PICP) In postmenopausal women, bone formation markers did not decrease with age When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -022, p < 005) and explained only 5-8% of the bone turnover variance (p < 001-0001) These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate

Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis

Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.

Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol.

Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor.

Over the past 55 years, two longitudinal studies have been monitoring the drinking behaviors and their consequences of several hundred men from adolescence and early adulthood to old age. The studies identified co-occurring sociopathy, cultural factors (e.g., ethnicity), and genetic factors (i.e., a family history of alcoholism) as risk factors for alcoholism. n most alcoholics, the disease had a progressive course, resulting in increasing alcohol abuse or stable abstinence. However, some alcoholics exhibited a nonprogressive disease course and either maintained a stable level of alcohol abuse or returned to asymptomatic drinking. Long-term return to controlled drinking, however, was a rare and unstable outcome. Formal treatment, with the exception of attending Alcoholics Anonymous, did not appear to affect the men's long-term outcomes, whereas several non-treatment-related factors were important for achieving stable recovery.

/pdf/the-natural-history-of-alcoholism-3097irph29.pdf

The Natural History of Alcoholism

The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation.

Hormonal characteristics of the human menstrual cycle throughout reproductive life.

• Serum cortisol response to the 1-mg overnight dexamethasone suppression test was studied in 221 depressed patients and 109 nondepressed psychiatric controls. Nonsuppression distinguished patients with primary unipolar depression (65/ 146) from patients with secondary unipolar depression (0/42) and nondepressed controls (0/109). Furthermore, nonsuppression distinguished the three familial subtypes of primary unipolar depressive illness: familial pure depressive disease (FPDD; 38/50 patients), sporadic depressive disease (SDD; 24/55 patients), and depression spectrum disease (3/41 patients). Moderate elevations in baseline serum cortisol levels were found in FPDD, SDD, and bipolar depression. Medication did not affect the results. The data suggest that the depressive syndrome is composed of separate illnesses, each of which has a distinctive pattern of hypothalamic-pituitary-adrenal axis activity during the depressed state as well as a specific clinical and familial psychiatric history.

https://jamanetwork.com/journals/PSYCH/articlepdf/492349/archpsyc_37_7_001.pdf

Hypothalamic-pituitary-adrenal axis activity in depressive illness. Its relationship to classification.

Hormonal characteristics of the human menstrual cycle throughout reproductive life

Blood levels of LH, FSH, estradiol (E2) and progesterone (P) were determined daily during 11 cycles in 4 women with a luteal phase of less than 10 days. In all cycles peak preovulatory estradiol levels were subnormal. Luteal phase secretion of both estradiol and progesterone was more than 2 sem below normal and mean, midfollicular phase FSH was lower than found in a group of normal cycles. In 2 individuals the defect was found to occur repetitively in cycles analyzed for up to 1 yr. All cycles were of normal total duration. The menstrual cycle with a short luteal phase may be a distinct and common form of infertility. When identified, it may be amenable to specific treatment with human chorionic gonadotropin or gonadotropin-releasing hormone.

Measurement of plasma LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the short luteal phase.

The LH and FSH responses to the administration of synthetic gonadotropin-releasing hormone (GnRH) were assessed in 14 patients with anorexia nervosa before, during and following weight gain. In 8 patients studied prior to therapy when they were at 53-64% of idal body weight, the LH response to GnRH was strikingly impaired while the FSH response was equal to that observed in normally menstruating women. After return to 79-88% of ideal body weight the LH response was improved but remained less than in the normal women. In a second group of 6 patients who were studied 4-11 months after hospital discharge when they were 90-94% of ideal body weight, the LH response was always equal to or greater than that found in the normal women. The serum estradiol concentration was low in all of the patients and remained less than 33 pg/ml even in those who returned to more than 90% of ideal body weight. Treatment with 25 mug of ethinyl estradiol for 3 days prior to repeat administration of GnRH did not result in a statistically significant increase of the LH or FSH responses above those before treatment. These data suggest changes occur in both hypothalamic and pituitary regulation of gonadotropin secretion in the course of nutritional rehabilitation of patients with anorexia nervosa and that synthesis and secretion of LH and FSH are modulated independently at the level of the pituitary gland.

Barry M. Sherman

Papers

Hormonal characteristics of the human menstrual cycle throughout reproductive life.

Hypothalamic-pituitary-adrenal axis activity in depressive illness. Its relationship to classification.

Hormonal characteristics of the human menstrual cycle throughout reproductive life

Measurement of plasma LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the short luteal phase.

LH and FSH response to gonadotropin-releasing hormone in anorexia nervosa: Effect of nutritional rehabilitation.