Higher Dehydroepiandrosterone Sulfate Levels Research Articles

Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome.

There is an inherited susceptibility to polycystic ovary syndrome (PCOS). Some investigators have suggested that premature male-pattern balding is a male phenotype in PCOS families, but this remains controversial. We recently reported evidence for an autosomal monogenic abnormality in ovarian and adrenal steroidogenesis in the sisters of women with PCOS. We performed this study to determine whether we could identify a clinical or biochemical phenotype in the brothers of women with PCOS. One hundred nineteen brothers of 87 unrelated women with PCOS and 68 weight- and ethnicity-comparable unrelated control men were examined and had fasting blood samples obtained. The odds of balding (Hamilton score > or = V) did not differ in the brothers of PCOS women compared with control men. Brothers of women with PCOS had significantly elevated dehydroepiandrosterone sulfate (DHEAS) levels [brothers 3035 +/- 1132 ng/ml (mean +/- SD) vs. control men 2494 +/- 1172 ng/ml; P < 0.05]. There was a significant positive linear relationship between DHEAS levels in PCOS probands and their brothers (r = 0.35; P = 0.001). There was no significant bimodal distribution in DHEAS levels, and there were no significant differences in other parameters in brothers of PCOS women with high DHEAS levels compared with those with low DHEAS levels. There is familial clustering of elevated DHEAS levels in the brothers of women with PCOS, suggesting that this is a genetic trait. This might reflect the same underlying defect in steroidogenesis that we found in the sisters of women with PCOS. Balding was not increased in the brothers of women with PCOS. We conclude that there is a biochemical reproductive endocrine phenotype in men in PCOS families.

DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years

Background: The objective of this study was to elucidate the associations of dehydroepiandrosterone sulfate (DHEA-S) levels and depressive symptoms in African American and Caucasian women in the late reproductive years, a transitional age zone preceding the perimenopause, in which ovarian aging and associated endocrine changes begin. We had hypothesized that lower levels of DHEA-S would be associated with depressive symptoms and that, because DHEA-S levels decline with increasing age, older women would have an increased prevalence of depressive symptoms. Methods: This cross-sectional study used a population-based urban sample recruited through random digit telephone dialing. The sample was 338 women between the ages of 35 and 47 years with regular menses. Half the sample was African American and half was Caucasian. Results: Higher DHEA-S levels were associated with depressive symptoms in women in the younger half of this cohort. Lower DHEA-S levels were associated with depressive symptoms in the women in the older half of this cohort. The direction of the relationship of DHEA-S and depressive symptoms changes with age, being a positive relationship in younger women and an inverse relationship in the older women in this cohort. This change in the direction of the relationship appears to occur at a younger age in African American women. Conclusions: Our hypothesis of a relationship between low DHEA-S levels and elevated depressive symptoms was supported only in the older women in this cohort. Unexpectedly, younger women in this cohort demonstrated a positive association between DHEA-S levels and depressive symptoms. Changes in DHEA-S levels, depressive symptoms, and the relationship of other hormones in the hypothalamic-pituitary-adrenal axis need to be better understood in premenopausal women approaching perimenopause.

Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels.

Immunity to Plasmodium falciparum develops slowly in areas of endemicity, and this is often ascribed to poorly immunogenic or highly variant parasite antigens. However, among populations newly exposed to malaria, adults acquire immunity more rapidly than children. We examined the relationship between pubertal development and resistance to P. falciparum. During two transmission seasons in western Kenya, we treated the same cohort of young males to eradicate P. falciparum and then obtained blood smears each week for 4 months. We determined pubertal development by Tanner staging and by levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone in plasma. In multivariate and age-stratified analyses, we examined the effect of pubertal development on resistance to malaria. In both seasons (n = 248 and 144 volunteers, respectively), older males were less susceptible than younger males. Age-related decreases in the frequency and density of parasitemia were greatest during puberty (15- to 20-year-olds). DHEAS and testosterone were significant independent predictors of resistance to P. falciparum parasitemia, even after accounting for the effect of age. Fifteen- to 20-year-old males with high DHEAS levels had a 72% lower mean parasite density (P<0.01) than individuals with low DHEAS levels. Similarly, 21- to 35-year-old males with high DHEAS levels had a 92% lower mean parasite density (P<0.001) and 48% lower frequency of parasitemia (P<0.05) than individuals with low DHEAS levels. These data suggest that the long period needed to attain full immunity could be explained as a consequence of host development rather than as the requirement to recognize variant or poorly immunogenic parasite antigens.

Increased Adrenal Androgen Functioning in Children With Oppositional Defiant Disorder: A Comparison With Psychiatric and Normal Controls

To examine the relationship between adrenal androgens and aggression in children with oppositional and antisocial behavior and to compare their levels with those of psychiatric and normal controls. Dehydroepiandrosterone sulfate (DHEAS) was measured in 24 children with oppositional defiant disorder (ODD), 42 psychiatric controls (including 20 children with attention-deficit/hyperactivity disorder [ADHD]), and 30 normal controls. The children's parents filled out the Child Behavior Checklist (CBCL). Children with ODD had higher DHEAS levels than either the psychiatric control or normal control groups; DHEAS levels of the latter groups did not differ. Moreover, it was possible to classify children as having either ODD or ADHD on the basis of their DHEAS levels, whereas this was not the case on the basis of the CBCL data. The results indicate that adrenal androgen functioning is specifically elevated in children with ODD. It is speculated that the mechanism could be a shift in balance of ACTH-beta-endorphin functioning in the hypothalamic-pituitary-adrenal axis due to early stress or genetic factors.

Characterization of serum dehydroepiandrosterone secretion in golden hamsters.

Dehydroepiandrosterone (DHEA) is an adrenal androgen whose function is poorly understood. Although DHEA and DHEA sulfate (DHEAS) are secreted in relatively high quantities by the human adrenal, the laboratory rat secretes very little, thus hindering experimental studies of the hormone. In this paper, we measured the changes in serum DHEA and DHEAS under various physiological conditions in golden hamsters. Evening serum DHEAS fell from 6.30 +/- 0.78 microg/dl (mean +/- SE) before surgery to 3.03 +/- 0.23 microg/dl 12 days after bilateral adrenalectomy. Hamsters had higher levels of DHEA and DHEAS in the evening than in the morning, but removal of the gonads did not consistently decrease serum DHEA or DHEAS in males or females. Evening levels of DHEA and DHEAS reached a peak around 7 weeks of age and then gradually decreased to about one-third of these levels by one year of age. These results suggest that DHEA and DHEAS are secreted at least in part from the hamster adrenal, that they do not originate from the gonads, and that there is a daily rhythm with peak levels at a time of day just preceding the active phase. In addition, the levels of these hormones decrease with aging.

Dehydroepiandrosterone sulfate and psychiatric measures in a frail, elderly residential care population

Background: Previous reports have found low levels of dehydroepiandrosterone sulfate (DHEA-S) in association with physical illness, and with frailty in the elderly. In a preliminary study, we also found low DHEA-S associated with increased disability and number of pain sites. However, we found the opposite relationship between DHEA-S and cognitive impairment. Therefore, we conducted a study of a second sample to confirm this unexpected finding and the expected inverse correlations between DHEA-S levels and increased disability and number of pain sites. Methods: Psychiatric symptoms and disorders were correlated with DHEA-S and related steroid levels in a second convenience sample in the nursing home population. Results: This sample confirmed the previous finding of a positive association of cognitive impairment with higher DHEA-S levels but the inverse association of DHEA-S levels with the numbers of pain sensations did not reach statistical significance. Cognitive impairment was also positively associated with higher dehydroepiandrosterone (DHEA) and estradiol levels (women only). Cortisol levels were inversely associated with depressive symptoms. Conclusions: The anomalous positive correlation between cognitive dysfunction and DHEA-S levels, and the inverse correlation between cortisol levels and depressive symptoms, suggests that the relationships between psychiatric symptomatology and levels of steroids that are part of the hypothalamic–pituitary adrenal axis are different in the frail elderly population from that of younger and heartier populations.

Relationships among cortisol (CRT), dehydroepiandrosterone-sulfate (DHEAS), and memory in a longitudinal study of healthy elderly men and women

At test times 18 months apart (Time 1 and Time 2), men (n Time 1 = 31, Time 2 = 23), women estrogen-users (n Time 1 = 14, Time 2 = 10), and women estrogen non-users (n Time 1 = 41, Time 2 = 27), whose average age was 72.1 and 73.4 years at Time 1 and Time 2, respectively, were tested with a battery of neuropsychological tests measuring verbal memory, visual memory, concentration/attention, language fluency and semantic memory. Plasma levels of CRT and DHEAS were assayed by radioimmunoassay at both test times. The men had higher DHEAS levels than both groups of women at both test times (p < 0.001) and also had a higher DHEAS/CRT ratio compared to the estrogen non-users (p < 0.05). Although there were no group differences in CRT levels at either time, CRT levels increased in the estrogen non-using women from Time 1 to Time 2 (p < 0.001). Subjects with lower CRT levels performed better than those with higher levels on several tests of declarative memory (p < 0.05). Men and estrogen-users had higher Digit Span scores compared to female estrogen non-users at both test times (p < 0.01), and women estrogen-users also had higher Backward Digit Span scores than non-users (p < 0.05). Both groups of women performed better than men on Category Retrieval (p < 0.01). These findings suggest that higher CRT levels in elderly men and women are associated with poorer explicit memory functioning; however, these results failed to provide any evidence that DHEAS is protective against declarative memory decline with aging.

Relation of Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate with Cardiovascular Disease Risk Factors in Women: Longitudinal Results from the Massachusetts Women’s Health Study

Low circulating levels of the adrenal steroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are thought to be associated with increased risk of cardiovascular disease (CVD) in men. In women, either a positive or null association with CVD has been found. The nature of the relation between DHEAS and CVD risk factors in women is unclear and is based on cross-sectional data. We present results from a longitudinal investigation of serum DHEA and DHEAS and cardiovascular disease risk factors in 236 women, initially 50–60 years old, from a population-based prospective (1986–1995) study of the menopausal transition. We used generalized estimating equations to model the relation of serum DHEA and DHEAS to systolic and diastolic blood pressure and serum levels of total cholesterol, high density lipoprotein cholesterol, and apolipoproteins A and B, adjusting for other factors related to CVD. Both DHEA and DHEAS were positively related to diastolic and systolic blood pressure, and DHEAS was negatively related to apolipoprotein A. DHEA and DHEAS were also positively related to smoking, alcohol use, estrone, and estradiol levels, and inversely related to age. Our results suggest that higher levels of DHEA and DHEAS in middle-aged women may indicate increased CVD risk.

Dehydroepiandrosterone Sulfate (DHEA-S) and Psychiatric and Laboratory Measures of Frailty in a Residential Care Population

Previous reports have found low levels of dehydroepiandrosterone sulfate (DHEA-S) in association with frailty in elderly patients. The mechanisms underlying these associations are not known. Therefore, psychiatric symptoms and disorders that are common in frail elderly patients were correlated with DHEA-S levels in a convenience sample selected from a nursing home population. Low DHEA-S levels were associated with high degrees of self-rated disability and insomnia. In women, low DHEA-S levels were also associated with increased numbers of pain sites. However, cognitive impairment was associated with higher DHEA-S levels in women. Thus, in frail elderly patients, there are contradictory relationships between DHEA-S and neuropsychiatric measures of frailty (cognitive impairment, disability, insomnia, and number of pain sites), and there may also be gender differences in these relationships.

Plasma dehydroepiandrosterone sulfate in unipolar major depression. Short communication.

We investigated plasma dehydroepiandrosterone sulfate (DHEAS) and cortisol levels in 12 patients with unipolar depression and 11 matched normal controls. The depressed patients showed significantly higher values of plasma DHEAS and cortisol than the controls. After 4 weeks of treatment with antidepressants (mainly clomiplamine), the high plasma DHEAS levels recovered. This finding showed the possible relationship between plasma DHEAS levels and depression, as well as cortisol levels.

DHEA-S selectively impairs contextual-fear conditioning: Support for the antiglucocorticoid hypothesis.

The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid properties, then its effects on fear conditioning might resemble those produced by adrenalectomy. The authors now report that chronic exposure to high levels of dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on auditory-cue fear conditioning. Preexposure to the context before drug treatment eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy, DHEA-S exerted its effect by interfering with the construction of a contextual memory representation. Thus, DHEA appears to act as a functional antiglucocorticoid in the processes that mediate learning and memory.

DHEA-S selectively impairs contextual-fear conditioning: support for the antiglucocorticoid hypothesis.

The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid properties, then its effects on fear conditioning might resemble those produced by adrenalectomy. The authors now report that chronic exposure to high levels of dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on auditory-cue fear conditioning. Preexposure to the context before drug treatment eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy, DHEA-S exerted its effect by interfering with the construction of a contextual memory representation. Thus, DHEA appears to act as a functional antiglucocorticoid in the processes that mediate learning and memory.

The epidemiology of DHEAS and cardiovascular disease.

In 1986 we reported that high levels of plasma dehydroepiandrosterone sulfate (DHEAS) reduced the risk of fatal cardiovascular disease (CVD) in 242 men and increased the risk in 289 women from the Rancho Bernardo cohort who were followed up for 12 years. We report here an update on the epidemiology of DHEAS and CVD based on a 19-year follow-up of 1,029 men and 942 women aged 30-88 years from the same cohort. In cross-sectional analyses, DHEAS levels decreased with age in both sexes and were lower in women than men. Men who were overweight were more likely to have low DHEAS levels; women who had hypercholesterolemia or hypertension or were nonusers of estrogen therapy had higher DHEAS levels. Alcohol intake and cigarette smoking were associated with higher DHEAS levels in both sexes. All differences were no longer statistically significant after adjusting for alcohol intake. All participants were followed for vital status. After 19 years there were 254 CVD deaths in men and 199 CVD deaths in women. DHEAS was not associated with CVD or ischemic heart disease (IHD) deaths in age-adjusted analyses where the comparison group was individuals without CVD or IHD death. In contrast, when the comparison group was survivors, multiply adjusted models showed a statistically significant, modestly reduced risk of fatal CVD (RR = 0.85) in men and a nonsignificant increased risk of fatal CVD (RR = 1.11) in women.

Dehydroepiandrosterone sulfate does not predict cardiovascular death in postmenopausal women. The Rancho Bernardo Study.

High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a reduced risk of fatal cardiovascular disease (CVD) in men. We examined the association between baseline DHEAS levels and the 19-year CVD and ischemic heart disease (IHD) mortality rates in 942 postmenopausal women free of known heart disease at baseline. The 199 CVD deaths and 102 IHD deaths were not related to baseline DHEAS levels. DHEAS was not related to body mass index, fasting plasma glucose, or family history of coronary heart disease, but significantly higher DHEAS levels were found in women who had elevated total or HDL cholesterol or blood pressure, were current smokers, or were nonusers of estrogen replacement therapy. After we adjusted for age, cholesterol, blood pressure, smoking, estrogen replacement therapy, obesity, fasting plasma glucose, and family history of heart disease, the relative risk of fatal CVD and IHD was 1.11 (95% confidence interval, 0.81 to 1.23) and 0.92 (95% confidence interval, 0.85 to 1.17), respectively, for a 50-microgram/dL decrease in DHEAS. Although higher DHEAS levels were associated with several major CVD risk factors, they were unrelated to the risk of fatal CVD in women.

Dehydroepiandrosterone sulfate and the risk of myocardial infarction in US male physicians: a prospective study.

High levels of dehydroepiandrosterone sulfate (DHEAS) have been associated with decreased risks of cardiovascular disease. The authors analyzed DHEAS in plasma collected at baseline among 169 participants in the Physicians' Health Study who subsequently had a myocardial infarction and 169 matched controls. The mean prediagnostic plasma DHEAS levels between cases (p = 0.33) (mean, 3.54 mumol/liter; standard deviation, 2.30) and controls (mean, 3.61 mumol/liter; standard deviation, 2.16) did not differ significantly. The relative risk was 1.04 (95 percent confidence interval 0.42-2.60) comparing extreme quintiles after adjustment for several coronary risk factors. In conclusion, these findings do not support the hypothesis that elevated plasma DHEAS is associated with a decreased risk of coronary disease in men, but a small to moderate association cannot be excluded.

CIRCULATING HORMONES IN PATIENTS WITH TONGUE CANCER

Serum FSH, LH, prolactin and plasma estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were estimated by RIA method in male patients with tongue cancer (N=110) and in healthy age-matched male controls (N=25). In this retrospective study, there was a trend towards higher levels of FSH (P<0.01), LH (P<0.01), prolactin (P<0.001), estradiol (P<0.0001), progesterone (P<0.0001) and DHEA (P<0.01) with concomitant lower levels of testosterone (P<0.001) and DHEA-S (P<0.02) in patients with tongue cancer compared to controls. We did not find significant difference in hormone levels when grouped according to the site of the tumor and stage of the disease. Patients below 40 years of age had significantly higher levels of DHEA and DHEA-S and lower levels of FSH than their counterparts. We observed a decreased ratio of testosterone: estradiol and increased levels of FSH, LH and prolactin in tongue cancer patients. These hormonal abnormalities clearly suggest a disturbance in the pituitary-adrenal-testicular axis. Based on our previous work and from these results, we suggest that prolactin might be playing an important role in the development and progression of tongue cancer.

Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study

We investigated the role of adrenal androgens, cortisol, testosterone and sex-hormone binding globulin (SHBG) as coronary risk factors using a nested case-control design. The study population consisted of 62 cases with cardiac endpoints and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls ( P < 0.04). DHEAS levels were positively associated with smoking ( P < 0.001), alcohol consumption ( P < 0.04) and triglyceride levels ( P < 0.002) and with systolic ( P < 0.04) and diastolic ( P < 0.006) blood pressures, and negatively associated with age ( P < 0.01) and HDL-cholesterol ( P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors - age, smoking, blood pressure, and lipid levels — as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confined to older men (odds ratio (OR) 7.3, 95% CI 2.3–23.3). A similar analysis with smoking revealed that the DHEAS-related risk was mainly found in smokers (OR 3.4, 95% CI 1.5–8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population.

Serum gonadal steroid hormones in young schizophrenic patients

Psychosis is reported to show a later age of onset in women than in men and its nature and course in women may also differ. The purpose of this study was to determine if levels of four steroid hormones at the start of early onset psychosis differ from the levels of other groups of young people and if predicted low levels of estrogen (E2) are a feature of female psychosis. Two blood samples from 22 young psychotic patients were analysed by radioimmunoassay for E2, progesterone (PROG), testosterone (TE), and dehydroepiandrosterone sulphate (DHEAS). Female psychotic patients showed E2 levels lower than matched healthy cycling controls but higher than those on a contraceptive pill; they also showed higher TE levels than controls. Male psychotic patients had higher DHEAS levels than healthy or obsessive compulsive disorder (OCD) subjects. We suggest that illness-related changes of steroids can be measured superimposed on medication-induced changes and that lower E2 levels in psychotic women may increase their vulnerability to psychosis. Changes of TE in female and DHEAS in male psychotics may be more a consequence of the illness.

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Adrenal and ovarian steroid hormone responses to gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome

It has been postulated that in polycystic ovary syndrome ovarian steroids can influence adrenal steroidogenesis. To test this hypothesis, basal and dexam ethasone-suppressed-corticotropin-stimulated steroid hormone responses were compared among three groups of women before, during, and after gonadotropin-releasing hormone agonist treatment for 3 months. The groups were characterized as follows: (1) women with polycystic ovary syndrome with high dehydroepiandrosterone sulfate levels (>400 [,g/dl), (2) women with polycystic ovary syndrome with normal dehydroepiandrosterone sulfate levels (&#x0026;#x003C;300 Rgldl), and (3) normal ovulatory women. In response to gonadotropin-releasing hormone agonist, basal serum luteinizing hormone, follicle-stimulating hormone, estradiol, estrone,17-hydroxyprogesterone, androstenedione, and testosterone in all three groups were suppressed to similar levels. Basal serum dehydroepiandrosterone sulfate levels in the group with high levels declined, but they did not reach the normal, unaltered concentrations in the other two groups. Two subjects with polycystic ovary syndrome in this group with high levels, who showed the greatest declines in basal serum dehydroepiandrosterone sulfate levels (34%, 40%), also had evidence of 3β-hydroxysteroid dehydrogenase deficiency before treatment, which was resolved by the end of treatment. In both groups with polycystic ovary syndrome, the increase in maximum incremental rise of dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in response to a pharmacologic dose of corticotropin from a dexam ethasone-suppressed baseline (adrenal androgen capacity) remained unaltered during gonadotropin-releasing hormone agonist administration. We conclude that ovarian steroids may promote excessive adrenal androgen secretion in women with polycystic ovary syndrome, may induce 3β-hydroxysteroid dehydrogenase deficiency as a mechanism for adrenal involvement in some women with polycystic ovary syndrome, and do not influence adrenal androgen capacity.