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Biomedical subjects

S L Berga

Publications and source records attributed to S L Berga.

At least 19 recordsLinked to original sources

Endocrine and chronobiological effects of fasting in women.

OBJECTIVE: To determine whether fasting in women would suppress GnRH/LH drive in a high- versus low-gonadal steroid milieu. DESIGN: Case-control study. SETTING: Academic clinical research center. PATIENT(S): Eleven eumenorrheic women and eleven women taking combined oral contraceptives. INTERVENTION(S): Seven of the eleven women in each group underwent an acute 72-hour fast. Blood samples were obtained at 15-minute intervals for 24 hours before the fast and during the last 24 hours of fasting. MAIN OUTCOME MEASURE(S): Twenty-four-hour profiles of LH, cortisol, and melatonin were assessed. Ovarian activity was tracked with estradiol and progesterone levels, and metabolic responses were gauged by measuring thyroid hormone and beta-hydroxy-butyric acid levels. RESULT(S): Fasting increased beta-hydroxy-butyric acid and reduced free thyronine. Fasting in the midfollicular phase had no effect on LH pulsatility or on FSH, estradiol, or subsequent luteal-phase progesterone levels. However, fasting elevated cortisol and resulted in a phase advance in melatonin secretion of 81 minutes in both the midfollicular and luteal phases. CONCLUSION(S): Fasting in women elicited expected metabolic responses and apparently advanced the central circadian clock without compromising reproductive function.

3-Hydroxybutyric Acid↗

Psychological correlates of functional hypothalamic amenorrhea.

OBJECTIVE: To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. DESIGN: Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

Adaptation, Psychological↗

Cognitive function and reproductive hormones in adjuvant therapy for breast cancer: a critical review.

Deterioration in cognitive function-particularly learning, memory, and attention-has been reported by women with breast cancer who receive adjuvant chemotherapy. Deficits in cognitive function reported by women with breast cancer are similar to those experienced by women as a consequence of natural or surgical menopause. The basis of these deteriorations may include reductions in reproductive hormone levels, particularly estrogens and progesterones, that occur as a result of adjuvant chemotherapy. This paper critically examines the literature related to the impact of adjuvant chemotherapy and reproductive hormone changes on cognitive function in women with breast cancer and suggests direction for future research in this area. The paper proposes a framework for investigation of the problem and discusses the challenges associated with the conduct of this research.

Antineoplastic Agents↗

Neuromodulation in polycystic ovary syndrome.

Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.

Female↗

Influence of estrogen replacement therapy on cardiovascular responses to stress of healthy postmenopausal women.

Two experiments were conducted to understand the influence of estrogen exposure on cardiovascular responses to acute stress measured by impedance cardiography. Study I compared stress responses of 29 postmenopausal women who used postmenopausal hormone replacement therapy (HRT) and 29 who did not use HRT. Women who did not use HRT had higher systolic blood pressure and pulse pressure responses to the tasks relative to HRT users. Study 2 compared stress responses of 38 healthy postmenopausal women not initially on HRT who were randomly assigned to transdermal estradiol or placebo treatment for 6-8 weeks. HRT assignment did not influence substantially women's cardiovascular responses to stress. Characteristics correlated with HRT use, not HRT itself, or differences in type, duration, and dosage may account for the discrepancy in results.

Estrogen Replacement Therapy↗

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.

Binding, Competitive↗

Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults.

OBJECTIVE: To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers. DESIGN: Randomized, controlled open trial. INTERVENTION: Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels. STATISTICAL ANALYSES PERFORMED: Group-by-time analysis of variance with repeated-measures, chi 2 test. RESULTS: Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men). The milk group gained 0.6 kg more than control group (P < .01); however, weight gain was less than predicted, which suggests some compensation for the added energy from milk. Blood pressure decreased similarly over time in both groups. Total and low-density lipoprotein cholesterol levels, and the ratio of total cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride levels increased within the normal range in the milk group (P = .002). Quality of life scores were high at baseline and remained high throughout. APPLICATIONS/CONCLUSIONS: Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice.

Aged↗

Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

OBJECTIVE: Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. STUDY DESIGN: Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. RESULTS: Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. CONCLUSIONS: In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

Adolescent↗

Do polycystic-appearing ovaries affect the risk of cardiovascular disease among women with polycystic ovary syndrome?

OBJECTIVE: To determine if polycystic-appearing ovaries (PAO) are associated with differences in risk factors for cardiovascular disease among women with polycystic ovary syndrome (PCOS). DESIGN: Case-control sub-study. SETTING: Division of Reproductive Endocrinology, Magee-Womens Hospital. PATIENT(S): Women with PCOS (n = 63) and non-PCOS controls (n = 56). INTERVENTION: Transvaginal ultrasonography and single sample venipuncture. MAIN OUTCOME MEASURE(S): Ultrasound ovarian appearance, fasting insulin, lipoproteins, androgens, LH/FSH ratio, anthropomorphic measurements, and blood pressure. RESULT(S): Women with PCOS had higher androgen and fasting insulin levels, a more adverse lipid profile, greater waist-hip and LH/FSH ratios, and a larger ovarian volume than controls. Thirty-three percent of the cases with PCOS, but only 5% of controls, showed PAO on ultrasound study (P<.01). PCOS cases with and without PAO had comparable levels of fasting insulin, lipids, and blood pressures. PCOS cases with PAO had a higher LH/FSH ratio (P=.028), increased levels of serum androstenedione (P=.029) and testosterone (P=.055), and greater ovarian volume (P=.024) compared to non-PAO patients. CONCLUSION: Women with PCOS have greater cardiovascular risk than controls. Within PCOS cases, however, the ultrasound appearance of polycystic ovaries does not appear to further intensify the cardiovascular disease risk profile of these women.

Adult↗

Dietary changes favorably affect bone remodeling in older adults.

OBJECTIVE: To determine whether dietary counseling to increase milk intake could produce useful changes in the calcium economy and what, if any, other nutrition-related changes might be produced. DESIGN: Randomized, open trial. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who habitually consumed fewer than 1.5 servings of dairy foods per day. Six academic health centers in the United States. INTERVENTION: Subjects were instructed to consume 3 servings per day of nonfat milk or 1% milk as a part of their daily diets, or to maintain their usual diets, for a 12-week intervention period, which followed 4 weeks of baseline observations. MAIN OUTCOME MEASURES: Energy and nutrient intake assessed from milk intake logs and 3-day food records; serum calciotrophic hormone levels at baseline and at 8 and 12 weeks; urinary excretion of calcium and N-telopeptide at 12 weeks. STATISTICAL ANALYSES: Repeated-measures analysis of variance. RESULTS: In the milk-supplemented group, calcium intake increased by 729 +/- 45 mg/day (mean +/- standard error), serum parathyroid hormone level decreased by approximately 9%, and urinary excretion of N-telopeptide, a bone resorption marker, decreased by 13%. Urine calcium excretion increased in milk-supplemented subjects by 21 +/- 7.6 mg/day (mean +/- standard error), less than half the amount predicted to be absorbed from the increment in calcium intake. All of these changes were significantly different from baseline values in the milk group and from the corresponding changes in the control group. Bone-specific alkaline phosphatase level (a bone formation marker) fell by approximately 9% in both groups. Serum level of insulin-like growth factor-1 (IGF-1) rose by 10% in the milk group (P < .001), and the level of insulin-like growth factor binding protein-4 (IGFBP-4) fell slightly (1.9%) in the milk group and rose significantly (7.9%) in the control group (P < .05). APPLICATIONS/CONCLUSIONS: The changes observed in the calcium economy through consumption of food sources of calcium are similar in kind and extent to those reported previously for calcium supplement tablets. The increase in IGF-1 level and the decrease in IBFBP-4 level are new observations that are beneficial for bone health. Important improvements in skeletal metabolism can feasibly occur in older adults by consumption of food sources of calcium. Dietitians can be confident that food works, and that desired calcium intakes can be achieved using food sources.

Aged↗

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.

Adult↗

The obstetrician-gynecologist's role in the practical management of polycystic ovary syndrome.

Women with polycystic ovary syndrome come to the gynecologist with a variety of symptoms, including menstrual irregularities, hirsutism, acne, weight gain, obesity, and infertility. An accurate diagnosis requires both confirmation of signs and symptoms of polycystic ovary syndrome and exclusion of other disorders. Once the diagnosis of polycystic ovary syndrome has been established, the presence of concomitant conditions, such as hypertension, dyslipidemia, and diabetes, must be assessed. Because the cause of polycystic ovary syndrome is not clear, treatment options have focused on symptom management. Such treatment options include oral contraceptives, gonadotropin-releasing hormone analogs with "add-back" hormone regimens, antiandrogens, ovulation-inducing agents, electrolysis, nutritional and weight loss counseling, exercise, laparoscopic ovarian drilling, and glucocorticoids. Pathogenic considerations, risk factor assessments, and treatment objectives combine to determine the choice of therapies. It is not clear whether insulin resistance is clinically important or causal in polycystic ovary syndrome symptom complex in all affected women. Polycystic ovary syndrome may be the final common expression of a variety of metabolic or neuroendocrine perturbations. If insulin resistance is a universal feature, it would make sense to treat with an insulin-sensitizing agent in the expectation that symptoms would resolve or improve. If insulin resistance is not the main etiologic factor, however, then insulin-sensitizing agents would be useful as adjunctive agents only for women with clinically important insulin resistance (eg, patients with polycystic ovary syndrome in whom insulin resistance causes hyperglycemia). In such cases an insulin-sensitizing agent could be instituted along with a program of weight loss and exercise.

Algorithms↗

Metabolic and endocrine effects of the desogestrel-containing oral contraceptive Mircette.

OBJECTIVE: The purpose was to evaluate the metabolic effects of Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol), a low-estrogen, desogestrel-containing oral contraceptive. STUDY DESIGN: Women taking Mircette were evaluated to determine its effects on lipid profiles (n = 74), carbohydrate metabolism (n = 25), and endocrine parameters (n = 53). RESULTS: During cycles 3 and 6 of Mircette treatment, changes from baseline included mean increases in serum triglycerides and very low-density lipoprotein cholesterol ranging between 50% and 60%. Smaller mean increases were observed at these time points in high-density lipoprotein cholesterol subfraction 2 (range between 17% and 25%), total cholesterol (<10%), high-density lipoprotein cholesterol (range between 10% and 15%), and high-density lipoprotein cholesterol subfraction 3 (range between 9% and 13%), with only nominal changes (<6%) in low-density lipoprotein cholesterol and lipoprotein. Patients receiving Mircette showed no mean changes in fasting plasma glucose or serum insulin levels but did have modest increases in glucose and insulin levels after a glucose challenge. Mircette treatment suppressed follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone to levels consistent with inhibition of ovulation and increased concentrations of thyroid- and cortisol-binding globulins. CONCLUSIONS: Overall, Mircette treatment was associated with expected effects on the pituitary-ovarian axis, triglycerides, and serum binding proteins; a modest decline in glucose tolerance; and a favorable effect on lipid profiles as a result of increases in total high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subfraction 2 in the absence of changes in total cholesterol or low-density lipoprotein cholesterol.

Adolescent↗

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.

Adult↗

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.

Adult↗

Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations.

OBJECTIVE: To test the hypothesis that increased cortisol secretion is specific to women with decreased GnRH drive and not found in eumenorrheic women or those with other causes of anovulation. DESIGN: Cortisol concentrations in blood were determined at 30-minute intervals for 24 hours in three well-characterized groups: women with functional hypothalamic amenorrhea, those with other causes of anovulation, and eumenorrheic women. SETTING: Academic medical center. PATIENT(S): Women aged 20 through 35 years, with well-defined reproductive states. INTERVENTION(S): Venous blood samples were obtained from, and psychometric inventories were completed by, the participants. MAIN OUTCOME MEASURE(S): Twenty-four-hour cortisol levels, 24-hour LH pulse patterns, and serial P levels were measured in women with functional hypothalamic amenorrhea, eumenorrheic women, and those with other causes of anovulation. RESULT(S): Cortisol secretion was higher in women with functional hypothalamic amenorrhea (n = 19) than in those with other causes of anovulation (n = 19) or eumenorrheic women (n = 19). Six women who recovered from functional hypothalamic amenorrhea had cortisol levels comparable to those of eumenorrheic women and those with other causes of anovulation. CONCLUSION(S): These data underscore the association between increased hypothalamic-pituitary-adrenal activity and reduced GnRH drive and support the concept that functional hypothalamic amenorrhea develops in response to stress-induced alterations in central neural function that modify hypothalamic function.

Adult↗