Neuropsychological functioning in girls with premature adrenarche.

Contemporary research indicates that brain development occurs during childhood and into early adulthood, particularly in certain regions. A critical question is whether premature or atypical hormone exposures impact brain development (e.g., structure) or function (e.g., neuropsychological functioning). The current study enrolled 40 girls (aged 6-8 years) diagnosed with premature adrenarche (PA) and a comparison group of 36 girls with on-time maturation. It was hypothesized that girls with PA would demonstrate lower IQ and performance on several neuropsychological tasks. The potential for a sexually dimorphic neuropsychological profile in PA was also explored. No significant univariate or multivariate group differences emerged for any neuropsychological instrument. However, effect size confidence intervals contained medium-sized group differences at the subscale level. On-time girls performed better on verbal, working memory, and visuospatial tasks. Girls with PA showed improved attention, but not a sexually dimorphic profile. These results, though preliminary, suggest that premature maturation may influence neuropsychological functioning.

Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet.

BACKGROUND: Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. METHODS: Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. RESULTS: Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. CONCLUSIONS: (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.

Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity.

We examined the contribution of 5-HT1A autoreceptors (with [11C]WAY100635 positron emission tomography) to amygdala reactivity (with blood oxygenation level-dependent functional magnetic resonance imaging) in 20 healthy adult volunteers. We found a significant inverse relationship wherein 5-HT1A autoreceptor density predicted a notable 30-44% of the variability in amygdala reactivity. Our data suggest a potential molecular mechanism by which a reduced capacity for negative feedback regulation of 5-HT release is associated with increased amygdala reactivity.

Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression.

The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome.

The diagnosis and treatment of stress-induced anovulation.

Behaviors that activate the hypothalamic-pituitary-adrenal (HPA) axis or suppress the hypothalamic-pituitary-thyroidal (HPT) axis can disrupt the hypothalamic-pituitary-gonadal (HPG) axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that serve as psychogenic stressors and present metabolic challenges. Complete recovery of gonadal function depends upon restoration of the HPA and HPT axes. Hormone replacement strategies have limited benefit because they do not promote recovery from these allostatic endocrine adjustments in the HPA and HPT axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only an alteration in the hypothalamic-pituitary-ovarian (HPO) axis. Further, use of sex hormones masks deficits that accrue from altered HPA and HPT function. Long-term deleterious consequences of stress-induced anovulation may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the HPA and HPT axes. Failure to reverse the hormonal milieu induced by stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes have the potential to permit resumption of ovarian function along with recovery of the HPT and HPA axes. Full endocrine recovery offers better individual, maternal, and child health.

Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects.

The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2,500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM; 19:00 to 21:00 h), or (3) dim (< 10 lux) red evening light (RED). In PMDD subjects, during the luteal phase compared to the follicular menstrual cycle phase, melatonin onset time was delayed, duration was compressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was decreased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the authors' previous observation that nocturnal melatonin concentrations are decreased in women with PMDD and suggest specific effects of light therapy on melatonin circadian rhythms that are associated with mood changes in patient versus control groups. The differential changes in onset and offset times during the menstrual cycle, and in response to AM and PM bright light compared with RED light, support a two-oscillator (complex) model of melatonin regulation in humans.

Blunted phase-shift responses to morning bright light in premenstrual dysphoric disorder.

Patients with premenstrual dysphoric disorder (PMDD) respond therapeutically to sleep deprivation and light therapy. They have blunted circadian rhythms of melatonin. The authors sought to test the hypothesis that these disturbances are a reflection of a disturbance in the underlying circadian pacemaker or, alternatively, that they reflect a disturbance in the input pathways to the clock. To test these hypotheses, after a 2-month diagnostic evaluation, 8 patients who met DSM-IV criteria for PMDD and 5 normal control (NC) subjects underwent two studies to determine whether PMDD subjects showed (1) altered melatonin sensitivity to light suppression (Study 1) and (2) altered phase-shift responses to morning light as a measure of the functional capacity of the underlying pacemaker (Study 2). In both studies, measurements were made during asymptomatic follicular and symptomatic luteal menstrual cycle phases in PMDD patients. The results of Study 1 showed no significant effect of group or menstrual cycle phase on the amount or percentage of suppression of melatonin by light. The results of Study 2 showed that with respect to the variable of offset time, PMDD subjects, when symptomatic, showed a reduced and directionally altered melatonin phase-shift response to a morning bright light stimulus; in 4 of 5 NC subjects, melatonin offset was advanced by bright morning light, whereas in PMDD subjects, it was delayed (3 subjects) or not shifted (5 subjects) (group effect, p = .045). Study 2 also revealed that area under the curve also changed differentially in PMDD versus NC subjects. In summary, the primary findings from this pilot study suggest that in PMDD there is a maladaptive (directionally altered and blunted) response to light in the symptomatic luteal phase. Because the suppressive effects of light were similar in PMDD and NC subjects, the previously observed low melatonin levels in this disorder do not likely represent a disturbance in pineal reactivity to suprachiasmatic nucleus efferents. Instead, the findings support a possible disturbance in PMDD in the clock itself or its coupling mechanisms.

Resistance of gonadotropin releasing hormone drive to sex steroid-induced suppression in hyperandrogenic anovulation.

Women with hyperandrogenic anovulation (HAA) exhibit increased GnRH drive, as evidenced by a faster LH pulse frequency that slows in response to progestin-induced opioidergic tone. To determine whether increased GnRH-LH drive in HAA reflects altered sex steroid exposure caused by chronic anovulation or is an intrinsic hypothalamic attribute, we compared the pulsatile LH response to oral contraceptive (OC)-induced suppression in seven women with HAA, with that of seven eumenorrheic women (EW). LH levels were determined at 10-min intervals for 12 h after 19-21 days of OC use and 5-7 days after cessation. Testosterone, androstenedione, estradiol, FSH, and LH levels were determined at weekly intervals before, during, and after OC use. LH pulse number/12 h was higher (P < 0.001) in HAA during and after OCs, when compared with that of EW. Mean LH was increased in HAA before, during, and after OCs. Testosterone, androstenedione, and estradiol levels were higher in HAA before OCs, but they decreased to similar levels during OC use in both groups. FSH concentrations were similar before and during OCs but rose more after cessation of OCs in EW. These findings indicate that GnRH drive in HAA is resistant to OC-induced suppression and, therefore, could be an intrinsic hypothalamic attribute.

Metabolic effects of oral contraceptives in women with polycystic ovary syndrome.

Insulin resistance and dyslipidemia have been described in women with polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism and oligomenorrhea. Although oral contraceptives (OC) are often instituted to regulate menses and suppress HA in women with PCOS, their use has been postulated to cause a deterioration in insulin sensitivity and to adversely affect circulating lipids. To investigate these effects, 9 women with PCOS and 10 age- and weight-matched control women were studied before and during the third month of therapy with a low-dose norethindrone-containing triphasic combination OC using the hyperglycemic clamp technique. At baseline, the PCOS group had higher androgen, triglyceride, and glycosylated hemoglobin concentrations, with a greater insulin response to oral glucose and a lower insulin sensitivity index (ISI) than controls. During OC therapy, a reduction in ISI was observed in both groups, whereas an increase in triglycerides was observed only in controls, removing any observed difference between the two groups in ISI or lipids. In women with PCOS, an increase in insulin concentrations during hyperglycemia accounted for the decline in ISI (P = 0.026), whereas in control women the decrease in ISI was attributable to a decrease in glucose disposal (P = 0.004). In conclusion, PCOS is characterized by insulin resistance in the untreated state. Short-term therapy with a triphasic OC results in a further decline in ISI in women with PCOS, without inducing additional adverse effects on lipids. A more pronounced decline in ISI together with an elevation in triglyceride levels occurs in normal women with OCs. The mechanisms leading to this decrease in ISI are different for each group.

Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea.

Plasma melatonin levels were determined by a sensitive RIA at 30 min intervals for 24h in 7 women with functional hypothalamic amenorrhea (HA) and in 7 age and season matched normal cycling women in the early follicular phase (NC). While daytime melatonin concentrations were nondetectable in both groups, the integrated nocturnal levels were 3-fold greater in HA (244 +/- 58 (SE) vs 74 +/- 32 pmol-min/Lx10(3), p less than 0.005). This melatonin increase in HA was due to an elevated peak amplitude (p less than 0.01) and extended duration (p less than 0.05). The latter was mostly due to a significant delay in the offset time of the amplified nocturnal melatonin secretion.

Increased luteinizing hormone and alpha-subunit secretion in women with hyperandrogenic anovulation.

Women with hyperandrogenic anovulation (HAA) have increased circulating levels of LH relative to those of FSH. The cause of this disturbance in gonadotropin secretion is uncertain. Previous investigations have sought to determine if increased GnRH drive is responsible for the excessive LH concentrations. Because previous results have conflicted, we addressed this question by comparing the 24-h secretory patterns of alpha-subunit and LH in women with HAA (n = 9) to those in eumenorrheic women in the midfollicular phase (n = 9). The mean (+/- SEM) pulse frequency was increased in women with HAA compared to that in eumenorrheic women of comparable age and percent ideal body weight for both LH (23.0 +/- 0.7 pulses/24 h vs. 3 17.1 +/- 1.7; P = 0.002) and alpha-subunit (23.0 +/- 0.8 vs. 19.1 +/- 1.2; P = 0.02). LH and alpha-subunit, but not FSH, responses to a submaximal dose of exogenous GnRH were increased in HAA, as were basal LH and alpha-subunit levels (P < 0.01). The present observations provide evidence for increased GnRH drive, including pulse frequency, in HAA. Although the results confirm the presence of a disturbance in gonadotropin secretion and suggest that its proximate cause may be of hypothalamic origin, they do not exclude the possibility that other factors, perhaps of ovarian origin, play a role in the establishment and/or maintenance of the altered gonadotropin secretory patterns and the chronic anovulation characteristic of HAA.

Ovarian responses in women to recombinant follicle-stimulating hormone and luteinizing hormone (LH): a role for LH in the final stages of follicular maturation.

During the follicular phase of the menstrual cycle, FSH stimulates follicular growth, granulosa cell aromatase activity, induction of LH receptors on the granulosa cell membrane, and estradiol secretion. As a result of negative feedback of estradiol on the pituitary, serum FSH concentrations decline. Despite the fall in FSH concentrations, the maturing follicle continues to develop to the preovulatory stage. In a prospective randomized trial, we tested the hypothesis that a key mechanism by which the dominant follicle continues to develop in the face of decreasing concentration of FSH is by acquiring LH responsiveness. In 24 women, pituitary gonadotropin secretion was down-regulated with a GnRH agonist. Follicular growth was then stimulated with recombinant human FSH (r-hFSH) until a 14-mm follicle was identified by ultrasound. The women were then randomized to 1 of 4 groups for a 2-day period: continued r-hFSH treatment, substitution of r-hFSH with saline, low dose r-hLH (150 IU, twice daily), or high dose r-hLH (375 IU, twice daily). Serum estradiol concentrations in the women receiving saline declined by the end of the 2-day randomization period. In contrast, serum estradiol concentrations continued to rise in women receiving either r-hFSH or r-hLH compared with those in the saline-treated group (P < 0.05). Pregnancies occurred in each of the gonadotropin treatment groups. These findings indicate that once FSH initiates follicular growth, either FSH or LH is capable of sustaining follicular estradiol production. Extrapolating these findings to the normal menstrual cycle suggests that the maturing follicle may continue to develop in the presence of diminishing FSH concentrations by acquiring the capacity to respond to LH.

Acceleration of luteinizing hormone pulse frequency in functional hypothalamic amenorrhea by dopaminergic blockade.

A constellation of neuroendocrine secretory aberrations, including reduced LH pulse frequency and PRL concentrations, has been documented in women with functional hypothalamic amenorrhea (FHA). As pituitary function was preserved, these aberrations were attributed to an alteration in hypothalamic neuromodulation. To investigate the participation of the dopaminergic system in the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA, we studied six women with FHA and six cyclic women in the early follicular phase by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h infusions of saline and a dopamine receptor blocker, metoclopramide (MCP). A hypothalamic vs. pituitary site of action was inferred from the pulsatility characteristics. MCP consistently elicited an increase in the LH pulse frequency in the women with FHA [7.3 +/- 1.2 (+/- SE) to 10.5 +/- 1.3 pulses/24 h; P less than 0.005]. In contrast, the eumenorrheic women did not show a significant change in LH pulse frequency in response to MCP (15.2 +/- 1.0 to 14.3 +/- 0.9 pulses/24 h). While the PRL concentrations were significantly lower in the FHA group during the infusion of saline (P less than 0.001) and MCP (P less than 0.005), the relative increases in PRL during MCP were similar in both groups. The acceleration of LH pulse frequency by blockade of dopamine receptors implies that there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency in women with FHA.

Neuroendocrine aberrations in women with functional hypothalamic amenorrhea.

To further elucidate the neuroendocrine regulation of anterior pituitary function in women with functional hypothalamic amenorrhea (FHA), we measured serum LH, FSH, cortisol, GH, PRL, TSH concentrations simultaneously at frequent intervals for 24 h in 10 women with FHA and in 10 normal women in the early follicular phase (NC). Using the same data, we separately analyzed the cortisol-PRL responses to meals in these women. In addition, the pituitary responses to the simultaneous administration of GnRH, CRH, GHRH, and TRH were assessed in 6 FHA and 6 normal women. The 24-h secretory pattern of each hormone except TSH was altered in the women with FHA. Compared to normal women, the women with FHA had a 53% reduction in LH pulse frequency (P less than 0.0001) and an increase in the mean LH interpulse interval (P less than 0.01); LH pulse amplitude was similar. The 24-h integrated LH and FSH concentrations were reduced 30% (P = 0.01) and 19% (P less than 0.05), respectively. The mean cortisol pulse frequency, amplitude, interpulse interval, and duration were similar in the two groups, but integrated 24-h cortisol secretion was 17% higher in the women with FHA (P less than 0.05). This increase was greatest from 0800-1600 h, but also was present from 2400-0800 h. Cortisol levels were similar in the two groups from 1600-2400 h, resulting in an amplified circadian excursion. In contrast, the 24-h serum PRL levels were markedly lower at all times (P less than 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P less than 0.05), and serum GH levels were increased at night in the women with FHA (P less than 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P less than 0.05) and T4 (P less than 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P less than 0.01) and dinner (P less than 0.05) and those of serum PRL to lunch (P less than 0.05) and dinner (P = 0.08) were blunted in the women with FHA. Pituitary hormone increments in response to the simultaneous iv administration of GnRH, CRH, GHRH, and TRH were similar in the two groups, except for a blunted PRL response to TRH in the women with FHA (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercortisolism in patients with functional hypothalamic-amenorrhea.

Hypercortisolism was found in patients with functional hypothalamic amenorrhea (HA) in preliminary short term studies conducted during the morning hours (0800-1100 h). This observation prompted us to characterize the circadian and pulsatile patterns of serum cortisol and LH levels at 15-min intervals for 24 h in 10 women with functional HA and in 7 normal women during the early follicular phase of their cycles. The mean integrated 24-h serum cortisol levels (area under the curve) were significantly (P less than 0.01) higher in the HA patients than in normal women. The mean cortisol levels in the HA patients were elevated (P less than 0.005) compared to those in the normal women during the daytime hours (0800-1600 h), but not during the evening (1600-2400 h) and sleeping hours (2400-0800 h). This selective hypercortisolism during the waking period of the day was almost entirely related to increased duration and amplitude of secretory episodes (peak area) rather than a change in pulse frequency. The serum cortisol increments in response to a noon meal that occurred in normal women were markedly impaired (P less than 0.01) in the HA patients. Compared with that in the normal women, mean LH pulse frequency was reduced by 30% in the HA patients. The 24-h mean LH levels and mean LH pulse amplitude were not significantly different from those in the normal women. However, among the HA patients there were marked individual differences in LH pulse frequency and amplitude, with prolonged interpulse quiescent periods, indicative of dysfunction of the hypothalamic GnRH pulse generator. We conclude that neuroendocrine activation of the ACTH-adrenal axis and inhibition of the GnRH pulse generator in women are associated with HA. Further, spontaneous resumption of normal cyclicity occurred in the majority (8 of 10) of the HA patients with no medical treatment, suggesting that this syndrome is a reversible hypothalamic disorder of a functional nature.

Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: a PET study.

BACKGROUND: Preclinical studies demonstrate that 17beta-estradiol (E(2)) increases serotonin-2A receptor (5-HT(2A)R) density in rat frontal cortex. METHODS: We investigated the impact of hormone replacement therapy on 5-HT(2A)R binding potential (BP) using positron emission tomography and [(18)F]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E(2), 0.1 mg/d, and following 2 to 6 weeks of E(2) plus micronized progesterone (P) 100 mg per os twice daily. Regional BPs in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were calculated by Logan analysis. RESULTS: There was a main effect of time (p = .017) for 5-HT(2A)R BP, which increased 21.2%+/-2.6% following combined E(2) and P administration relative to baseline. This effect was evident in all cerebral cortex regions examined. CONCLUSIONS: 5-HT(2A)R BP increased in widespread areas of the cerebral cortex following combined E(2) + P administration.

Morning versus evening bright light treatment of late luteal phase dysphoric disorder.

Six women with late luteal phase dysphoric disorder had a significant reduction in depression ratings after treatment with evening, but not morning, bright light. Bright light may offer an alternative to the pharmacologic treatment of premenstrual mood disorders.

Psychological stress and immunological responsiveness in normally cycling, follicular-stage women.

Nineteen women in the follicular stage of their menstrual cycles were assessed for immunological responsiveness to a 50-min series of three psychological tasks which reliably elicit cardiovascular and neuroendocrine stress responses. Ten follicular-stage women not subjected to stress served as controls. Stress decreased lymphocyte responsiveness to PHA and PWM, percent of CD4+ cells and the ratio of CD4+/CD8+ cells. Conversely, stress increased natural killer cell number and cytolytic activity, white blood cell, lymphocyte, T and B cell count. Except for natural killer cell number, none of these changes was exhibited by controls. Most of these stress responses are similar to those reported for men and form the basis for a continuing study of the effects of reproductive hormones and stress on cardiovascular and immunological function in women.

Effects of short-term suppression of ovarian hormones on cardiovascular and neuroendocrine reactivity to stress in women.

The present study reduced the levels of ovarian hormones to early postmenopausal levels by a GnRH agonist and evaluated the effects of a temporary suppression of ovarian hormones on premenopausal women's cardiovascular and neuroendocrine responses to laboratory challenges. The stress responses of 24 healthy young women were evaluated during three tasks during the early follicular phase and then after three monthly injections of Lupron, which suppressed their levels of estradiol, FSH, and LH. Thereafter, half the group resumed menstrual cycles (labeled Cycle), and half continued having Lupron injections in combination with transdermal estradiol (labeled Patch) and all were reevaluated a third time. A third group (labeled Control) of 12 women had four monthly injections of Lupron first and then were evaluated the first time. After their cycles resumed, they were reevaluated twice 3 months apart. Results showed that the magnitude of the blood pressure and catecholamine changes declined over the three evaluations, suggesting that the women's stress responses habituated. Although the suppression of ovarian hormone levels led to alterations in ovarian hormones for several months, which were accompanied by typical menopausal symptoms, cardiovascular and neuroendocrine responses to stress did not vary. This study did not test the effects of current estrogen exposure or of long term suppression of ovarian hormones upon cardiovascular and neuroendocrine responses.

Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study.

Polycystic ovary syndrome (PCOS), a disorder of hyperandrogenism and chronic anovulation affects 5%-10% of all women. Women with PCOS often have elevated cardiovascular risk factors. A total of 244 PCOS cases were identified through the Division of Reproductive Endocrinology at Magee-Womens Hospital and were age-matched to 244 neighborhood controls. The average age of cases and controls was 35.3 +/- 7.4 and 36.7 +/- 7.7. Women with PCOS compared to controls had substantially higher LDL-C and total cholesterol levels at each age group under 45 years after adjustment for body mass index, hormone use, and insulin levels. In the over 40-year age group, little difference was noted between cases and controls. Among cases and controls (<40), PCOS predicted LDL-C, total cholesterol and triglycerides, but did not have a significant effect on lipid levels in older cases and controls after controlling for the other variables. The primarily pre- to perimenopausal PCOS cases > or =40 years of age have similar LDL-C and total cholesterol levels as their age-matched controls, probably reflecting the LDL-C increase with age among controls.