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Sarah L Berga

Publications and source records attributed to Sarah L Berga.

18 recordsLinked to original sources
PubMed2006

Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

CONTEXT: The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. OBJECTIVE: We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). DESIGN: The study is a cross-sectional comparison. SETTING: The study was set in a general clinical research center at an academic medical center. PARTICIPANTS: Fifteen women with FHA who were of normal body weight and 14 EW participated. INTERVENTION: Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. MAIN OUTCOME MEASURES: Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. RESULTS: CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. CONCLUSIONS: The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

Amenorrhea↗
PubMed2006

Cognitive impairment associated with adjuvant therapy in breast cancer.

The purpose of this study was to determine whether cognitive function changes over time in women with breast cancer who received adjuvant therapy as compared to women with breast cancer who received no adjuvant therapy. Three groups of women (n = 46) were studied; groups 1 and 2 consisted of women with stage I or II breast cancer. Group 1 received chemotherapy and group 2 received chemotherapy plus tamoxifen. Group 3 consisted of women with ductal carcinoma in situ who received no chemotherapy or tamoxifen. Cognitive function was evaluated at three timepoints. Time 1 occurred after surgery and before chemotherapy initiation in groups 1 and 2. Time 1 for group 3 occurred post-surgery. Time 2 occurred within 1 week after the conclusion of chemotherapy for groups 1 and 2 and at a comparable time for group 3. Time 3 occurred 1 year after Time 2. Women who received chemotherapy plus tamoxifen exhibited deterioration on measures of visual memory and verbal working memory and reported more memory complaints. Women who received chemotherapy alone also exhibited deteriorations in verbal working memory. Conversely, cognitive function scores improved in women who received no therapy, indicating practice effects. In conclusion, adjuvant chemotherapy in women with breast cancer can be associated with deteriorations in memory and this may persist over time. The addition of tamoxifen may lead to more widespread memory deficits.

Adult↗
PubMed2006

Obesity distribution and reproductive hormone levels in women: a report from the NHLBI-sponsored WISE Study.

PURPOSE: Relationships between body weight and disease are not straightforward. Central obesity appears to be a relatively greater cardiovascular risk factor than generalized obesity. The purpose of this study was to evaluate body mass index (BMI) and waist circumference and the association of obesity distribution with blood estrogen levels (estradiol, bioavailable estradiol, and estrone). METHODS: The study cohort consisted of 207 postmenopausal women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) undergoing angiography for evaluation of suspected ischemia. RESULTS: Both BMI and waist circumference were positively associated with all three blood estrogen levels (p < 0.01), with the highest estrogen levels found in the obese women with large waists (p < 0.01). Results from regression analyses confirmed significant associations of BMI and waist circumference with the estrogen levels. CONCLUSIONS: These results demonstrate differing relationships between blood estrogen levels and obesity distribution in a cohort of postmenopausal women with chest pain undergoing coronary angiography. The differing levels by general and central obesity may help explain in part observed epidemiological relationships between obesity and disease.

Adult↗
PubMed2005

Influence of hormone therapy on the cardiovascular responses to stress of postmenopausal women.

Epidemiological and psychophysiological data suggest that groups that differ in reproductive hormones and stress responses also differ in risk for cardiovascular disease. To evaluate the effects of hormone therapy on women's cardiovascular responses to laboratory stressors, 89 healthy postmenopausal women were tested twice, before and after exposure for about 8 weeks to one of the five conditions: placebo, Estratab (primarily estrone), Estratab plus Prometrium (micronized progesterone), Estratab plus Provera (synthetic progestin), and Estratest (same estrogen as in Estratab plus methyltestosterone). Results showed that women assigned to Estratab plus Prometrium and Estratest had diminished systolic blood pressure responses to stress upon retesting, whereas the other groups did not change in the level of their responses. Women assigned to Estratab plus Prometrium had diminished diastolic blood pressure responses during a speech stressor upon retesting, whereas women assigned to Estratab plus Provera increased. Our findings show that hormone therapy does affect women's stress responses, but they do not provide a simple explanation as to why groups at high and low risk for cardiovascular disease differ in reproductive hormones and stress responses.

Arousal↗
PubMed2005

Sensitivity to stress-induced reproductive dysfunction linked to activity of the serotonin system.

OBJECTIVE: To use a nonhuman primate model and determine whether individuals sensitive to stress-induced reproductive dysfunction have lower activity of central serotonergic neurons under nonstressed conditions. DESIGN: The activity of the central serotonergic system was assessed by measuring responsiveness to a fenfluramine challenge (5 mg/kg, IV) in sedated monkeys previously categorized as highly stress resistant (HSR; n = 4; normal menstrual cyclicity through two stress cycles), medium stress resistant (MSR; n = 5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e., stress sensitive, SS; n = 4; anovulatory as soon as stress is initiated). To control for differences in pituitary stores of prolactin or ACTH, the animals were subsequently administered a bolus of thyrotropin-releasing hormone (3 microg/kg) plus corticotropin releasing factor (CRF), (3 microg/kg). SETTING: Oregon National Primate Research Center, Animal Services Building. PATIENT(S): Female cynomolgus macaques exhibiting normal menstrual cycles. INTERVENTION(S): Administration of fenfluramine, a serotonin-releasing drug. MAIN OUTCOMES MEASURE(S): Serum concentrations of prolactin (PRL) and cortisol (F). RESULT(S): Prolactin release in response to fenfluramine was significantly greater in the HSR group compared with the MSR or SS groups. In contrast, cortisol was higher in the SS group compared with the other two groups. Similar responses were not evident after thyrotropin-releasing hormone + CRF stimulation. CONCLUSION(S): The lower PRL response to fenfluramine in the stress-sensitive animals suggests that stress-sensitive individuals have decreased activity in central serotonergic neurons. However, the F data suggest that the hypothalamic-pituitary-adrenal axis in stress-sensitive individuals is highly responsive to even small increases in serotonin.

Animals↗
PubMed2004

Determination of menopausal status in women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

PURPOSE: Accurate classification of menopausal status is important to epidemiological research evaluating the role of reproductive hormones in disease processes. Algorithms relying on repeat hormone assays are unfeasible in large epidemiological studies. This paper summarizes the development of the Women's Ischemia Syndrome Evaluation (WISE) Hormonal menopausal status algorithm for determining premenopausal, perimenopausal, and postmenopausal status using menstrual and reproductive history and reproductive hormone levels obtained at a single clinic visit. METHODS: The authors compared the accuracy of this algorithm with two currently used self-report algorithms: Menstrual, based only on months since last menstrual period, and Historical, which adds age and surgical history. RESULTS: The study population consisted of 515 women (329 clearly postmenopausal) enrolled in the WISE study who were undergoing coronary angiography for suspected ischemia. A subgroup of 186, not clearly postmenopausal, was classified by these three algorithms. Results were evaluated against individualized expert consensus classification. The Menstrual and Historical classifications differed significantly (p < 0.0001) from expert consensus, with 32%-26% discordant classifications, respectively. For the WISE Hormonal classification, discordance was 4%. CONCLUSIONS: The authors conclude that inaccurate classifications of menopausal status occur frequently in self-report algorithms. Use of the relatively simple WISE algorithm can improve the accuracy of menopausal status classification for epidemiological research.

Adult↗
PubMed2003

Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study.

OBJECTIVES: We sought to evaluate hypoestrogenemia of hypothalamic origin and its association with angiographic coronary artery disease (CAD) in premenopausal women. BACKGROUND: Coronary artery disease in premenopausal women appears to have a particularly poor prognosis. Primate animal data suggest that premenopausal CAD is strongly determined by psychosocial stress-induced central disruption of ovulatory cycling and resulting hypoestrogenemia. METHODS: We assessed reproductive hormone blood levels and angiographic CAD using core laboratories in 95 premenopausal women with coronary risk factors who were enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation and were undergoing coronary angiography for evaluation for suspected ischemia. RESULTS: Premenopausal women with angiographic CAD (n = 13) had significantly lower estradiol, bioavailable estradiol, and follicle-stimulating hormone (FSH) (all p < 0.05) than women without angiographic CAD (n = 82), even after controlling for age. Hypoestrogenemia of hypothalamic origin, defined as estradiol <184 pmol/l (50 pg/ml), FSH <10 IU/l, and luteinizing hormone <10 IU/l, was significantly more prevalent among the women with CAD than those without CAD (9/13 [69%] vs. 24/82 [29%], respectively, p = 0.01). Hypoestrogenemia of hypothalamic origin was the most powerful predictor of angiographic CAD in a multivariate model (odds ratio [OR] 7.4 [confidence interval (CI) 1.7 to 33.3], p = 0.008). Anxiolytic/sedative/hypnotic and antidepressant medication use were independent predictors of hypoestrogenemia of hypothalamic origin in a multivariate model (OR 4.6 [CI 1.3 to 15.7], p = 0.02, OR 0.10 [CI 0.01 to 0.92], p = 0.04, respectively). CONCLUSIONS: Among premenopausal women undergoing coronary angiography for suspected myocardial ischemia, disruption of ovulatory cycling characterized by hypoestrogenemia of hypothalamic origin appears to be associated with angiographic CAD.

Adult↗
PubMed2003

Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women.

OBJECTIVE: To use statistical parametric mapping to determine the extent of previously reported serotonin type 2A (5HT(2A)) receptor binding potential (BP) increases in postmenopausal women following hormone therapy. DESIGN: Repeated measures positron emission tomography (PET) study. SETTING: Academic research environment. PATIENT(S): Five healthy, postmenopausal women. INTERVENTION(S): Serial PET images of [(18)F]altanserin uptake were acquired to measure 5HT(2A) receptor BP at menopausal baseline, following estradiol (E(2)), and following combined E(2) + micronized progesterone (P(4)). MAIN OUTCOME MEASURE(S): 5HT(2A) receptor BP. RESULT(S): Combined E(2) + P(4) treatment was associated with significant increases in the 5HT(2A) receptor BP increases in widespread areas of cerebral cortex. Treatment with E(2) alone was also associated with widespread cortical BP increases, although these changes reached statistical significance in fewer regions. The rate of [(18)F]altanserin metabolism was significantly decreased in the E(2) + P(4) condition relative to menopausal baseline, but this difference did not appear to correlate with changes in 5HT(2A) receptor BP. CONCLUSION(S): Estradiol priming followed by combined E(2) + P(4) is associated with widespread increases in 5HT(2A) receptor BP in the cerebral cortex, consistent with the E(2)-associated increases in 5HT(2A) receptor density previously observed in experimental animals.

Administration, Cutaneous↗
PubMed2003

Treatment of functional hypothalamic amenorrhea with hypnotherapy.

OBJECTIVE: To determine the effects of hypnotherapy on resumption of menstruation in patients with functional hypothalamic amenorrhea (FHA). DESIGN: Uncontrolled clinical study. SETTING: Academic clinical care center. PATIENT(S): Twelve consecutive women with FHA were selected. INTERVENTION(S): A single 45- to 70-minute session of hypnotherapy was administered, and patients were observed for 12 weeks. MAIN OUTCOME MEASURE(S): Patients were asked whether or not menstruation resumed and whether or not well-being and self-confidence changed. RESULT(S): Within 12 weeks, 9 out of 12 patients (75%) resumed menstruation. All of the patients, including those who did not menstruate, reported several beneficial side effects such as increased general well-being and increased self-confidence. CONCLUSION(S): Hypnotherapy could be an efficacious and time-saving treatment option that also avoids the pitfalls of pharmacological modalities for women with FHA.

Amenorrhea↗
PubMed2003

Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.

OBJECTIVE: To determine whether cognitive behavior therapy (CBT) targeted to problematic attitudes common among women with functional hypothalamic amenorrhea would restore ovarian function. DESIGN: Randomized, prospective, controlled intervention. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Sixteen women participated who had functional hypothalamic amenorrhea; were of normal body weight; and did not report psychiatric conditions, eating disorders, or excessive exercise. INTERVENTION(S): Subjects were randomized to CBT or observation for 20 weeks. MAIN OUTCOME MEASURE(S): Serum levels of E(2) and P and vaginal bleeding were monitored. RESULT(S): Of eight women treated with CBT, six resumed ovulating, one had partial recovery of ovarian function without evidence of ovulation, and one did not display return of ovarian function. Of those randomized to observation, one resumed ovulating, one had partial return of ovarian function, and six did not recover. Thus, CBT resulted in a higher rate of ovarian activity (87.5%) than did observation (25.0%), chi(2) = 7.14. CONCLUSION(S): A cognitive behavioral intervention designed to minimize problematic attitudes linked to hypothalamic allostasis was more likely to result in resumption of ovarian activity than observation. The prompt ovarian response to CBT suggests that a tailored behavioral intervention offers an efficacious treatment option that also avoids the pitfalls of pharmacological modalities.

Adult↗
PubMed2003

Menstrual cycle differences between women with type 1 diabetes and women without diabetes.

OBJECTIVE: To evaluate menstrual cycle histories among women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes across all reproductive ages. RESEARCH DESIGN AND METHODS: Menstrual and reproductive histories were obtained by questionnaire from 143 women with type 1 diabetes, 186 sisters without diabetes, and 158 unrelated control subjects without diabetes participating in the Familial Autoimmune and Diabetes study. RESULTS: Women with type 1 diabetes had more menstrual problems (long cycles, long menstruation, and heavy menstruation) before age 30 years than sisters and control subjects. These differences were all statistically significant, except for heavy menstruation at age <20 years. No differences were observed after age 30 years. Women with type 1 diabetes experienced later menarche, earlier natural menopause, fewer pregnancies, and more stillbirths than women without diabetes. Multiple regression analyses revealed that type 1 diabetes caused an approximate twofold increased risk of any menstrual problem before age 30 years. These were primarily related to long cycles and long menstruation in women aged <20 and 20-29 years, as well as with heavy menstruation from 20 to 29 years. Oral contraceptives were protective for any menstrual problem and heavy menstruation from 30 to 39 years of age. With history of pregnancy from 20 to 40 years of age, any menstrual problem and long menstruation were more likely. CONCLUSIONS: The results suggest that type 1 diabetes is an independent risk factor for menstrual disturbances in young adults. Future studies may determine whether addressing menstrual disturbances improves quality of life and health for these women.

Adult↗
PubMed2002

Cholesterol-lowering medication, cholesterol level, and reproductive hormones in women: the Women's Ischemia Syndrome Evaluation (WISE).

PURPOSE: Reproductive hormones such as estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway. We hypothesized that use of statins and the resultant lower blood lipoprotein levels would be associated with lower reproductive hormone levels in women. We also sought to evaluate this association, independent of statin use, particularly among premenopausal women of childbearing age. METHODS: We enrolled 453 (114 pre-, 30 peri-, and 309 postmenopausal) women with coronary risk factors (mean [+/- SD] age, 58 +/- 13 years) who were undergoing coronary angiography for suspected ischemia at four academic medical centers. Blood lipoprotein levels (total cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol) and serum reproductive hormone levels (estradiol, bioavailable estradiol, estrone, progesterone) were measured. RESULTS: Use of statins was associated with lower lipoprotein levels, but not lower reproductive hormone levels, in all women. Mean estradiol levels were not significantly lower among premenopausal women with very low LDL cholesterol levels compared with women with higher LDL cholesterol levels (estradiol: 71 +/- 52 pg/mL vs. 88 +/- 67 pg/mL, P = 0.32). CONCLUSION: Among women undergoing coronary angiography for suspected myocardial ischemia, the use of statins, or lower cholesterol levels, are not associated with significantly lower levels of reproductive hormones.

Adult↗
PubMed2002

Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma.

OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). METHODS: We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. RESULTS: Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. CONCLUSIONS: Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.

Adult↗
PubMed2002

Postmenopausal hyperthecosis: functional dysregulation of androgenesis in climacteric ovary.

BACKGROUND: Hyperandrogenism of ovarian origin is rare in postmenopausal women. However, there is evidence that the ovaries of postmenopausal women are active endocrine glands, secreting mainly androgens. CASE: A postmenopausal woman sought treatment for progressive hirsutism. Endocrine evaluation revealed androgen excess. Transvaginal ultrasound revealed enlarged ovaries. Hysterectomy and bilateral oophorectomy were recommended. However, surgery had to be withheld for 6 months while the patient recovered from an acute myocardial infarction. In the interim, the patient's hyperandrogenemia was successfully treated with monthly injections of the gonadotropin-releasing hormone agonist (GnRH), leuprolide acetate. CONCLUSION: This report illustrates the potential for postmenopausal ovaries to become active androgen-secreting endocrine organs. It also demonstrates the efficacy of pharmacologic intervention for postmenopausal ovarian hyperthecosis when the patient is a poor surgical candidate.

Algorithms↗
PubMed2002

Short-term suppression of ovarian function and immune measures in healthy women.

Ovarian function was suppressed to postmenopausal levels with a GnRH agonist for four months in healthy, premenopausal women to examine the effect of short-term alterations in sex steroid exposure on immune measures at rest and in response to standardized laboratory stressors. Twenty-two women were assessed at three times: (a) during the early follicular phase of the menstrual cycle; (b) after ovarian function had been suppressed by a GnRH agonist; and (c) either in the early follicular phase after the resumption of regular menstrual cycling (group labeled Cycle), or when women received estradiol transdermally in conjunction with a GnRH agonist (group labeled Patch). A third group of 11 women was assessed at similar time points, but in a different order of pharmacologic intervention to evaluate the effects of ovarian function suppression that were not confounded by habituation to the laboratory stressors (group labeled Hormone Control). Finally, 15 women served as control subjects to control for the effects of time, seasonality and blood collection procedures on immune measures (group labeled Immune Control). Immune measures included circulating cell counts, response to mitogens (PHA and PWM), and NK cytotoxicity. Results revealed no consistent changes in basal or stress-induced immune measures that varied with a period of short-term suppression of ovarian function. Basal and acute stress-induced cell counts showed moderate to high temporal stability over a six to ten month time interval.

Adult↗