Estherann Grace

Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa.

Bone loss is a serious consequence of anorexia nervosa (AN). Subnormal levels of serum dehydroepiandrosterone (DHEA) are seen in patients with AN and may be causally linked to their low bone density. We hypothesized that oral DHEA would decrease markers of bone resorption (urinary N‐telopeptides [NTx]), and increase markers of bone formation (serum bone‐specific alkaline phosphatase and osteocalcin [OC]). Fifteen young women (age 15–22 years) with AN were enrolled in a 3‐month, randomized, double‐blinded trial of 50, 100, or 200 mg of daily micronized DHEA. Blood and urinary levels of adrenal and gonadal steroids and bone turnover markers were measured. No adverse clinical side effects of DHEA were noted, and a 50 mg daily dose restored physiologic hormonal levels. At 3 months, NTx levels had decreased significantly in both the 50 mg (p = 0.018) and the 200 mg (p = 0.016) subgroups. OC levels simultaneously increased within treatment groups over time (p = 0.002). Eight out of 15 (53%) subjects had at least one menstrual cycle while on therapy. Short‐term DHEA was well‐tolerated and appears to normalize bone turnover in young women with AN. Resumption of menses in over half of subjects suggests that DHEA therapy may also lead to estradiol levels sufficient to stimulate the endometrium in this group of patients.

Sleep continuity and architecture: Associations with pain-inhibitory processes in patients with temporomandibular joint disorder

Recent research suggests bi‐directional interactions between the experience of pain and the process of sleep; pain interferes with the ability to obtain sleep, and disrupted sleep contributes to enhanced pain perception. Our group recently reported, in a controlled experimental study, that sleep fragmentation among healthy adults resulted in subsequent decrements in endogenous pain inhibition. The present report follows up that observation by extending this line of research to a sample of patients experiencing persistent pain. Patients with chronic temporomandibular joint disorder (TMD) pain were studied using polysomnography and psychophysical evaluation of pain responses. We assessed whether individual differences in sleep continuity and/or architecture were related to diffuse noxious inhibitory controls (DNIC), a measure of central nervous system pain inhibition. Among 53 TMD patients, higher sleep efficiency and longer total sleep time were positively associated with better functioning of DNIC (r = 0.42–0.44, p < 0.01; ps < 0.05 for the multivariate analyses). These results suggest the possibility that disrupted sleep may serve as a risk factor for inadequate pain‐inhibitory processing and hint that aggressive efforts to treat sleep disturbance early in the course of a pain condition might be beneficial in reducing the severity or impact of clinical pain.

Neuroanatomy of human appetitive function: a positron emission tomography investigation.

OBJECTIVE The mediating neuroanatomy of human appetitive function is poorly understood. A state induction paradigm was employed, in conjunction with positron emission tomography, to test the hypothesis that limbic/paralimbic regions respond to the desirability of food stimuli. METHODS Eight normal subjects were studied during each of three conditions, involving visual exposure to high-caloric food, low-caloric food, and nonfood stimuli. Subjective indices of hunger were measured via analog scales. RESULTS Planned contrasts demonstrated significant increases in desire to eat and decreases in left temporoinsular cortical blood flow during the high-caloric versus control conditions. DISCUSSION Results implicate the temporo-insular cortex in normal appetitive function, suggesting that activity within this region is associated with the desirability or valence of food stimuli, prior to ingestion. These data will provide a broad foundation for future studies of patients with eating disorders.

Factors associated with compliance to oral contraceptive use in an adolescent population

Because adolescents often do not use contraception effectively, this study was undertaken to determine the factors that affect oral contraceptive compliance. One hundred and one patients who chose oral contraceptives as their first method of birth control were interviewed. The results suggest that the most important factors associated with noncompliance are an age of 15-16 years at initiation of oral contraception, no plans to attend college, dissatisfaction with the clinic visit, the occurrence of side effects, and lack of parental involvement with the clinic visit. There was no association of compliance with prior pregnancy or parental knowledge of pill use. Contraceptive programs may be improved by addressing adolescent concerns regarding drug side effects, anticipating their reasons for discontinuing the pill, and following up frequently those adolescents at greatest risk for noncompliance.

The relationships of calculated percent body fat, sports participation, age, and place of residence on menstrual patterns in healthy adolescent girls at an independent new England high school

A prospective study was undertaken to determine normal menstrual patterns in healthy girls in an independent high school and assess the effects of exercise (type and hours per day), age (chronologic and gynecologic), calculated estimate of body fat, and place of residence (boarding and day students) on menstrual function. Three hundred twenty-seven girls (means age 15.5 +/- 1.1 years) answered a questionnaire on menstrual history; 306 (93.6%) were postmenarchal and 21 (6.4%) premenarchal. Calculated estimate of percent body fat was significantly lower in premenarchal than postmenarchal girls (22.4% versus 27.3% p less than 0.0001). Ninety-three percent of adolescents reported flow lasting 4-7 days; 59.7% dysmenorrhea; and 63% premenstrual symptoms. There was no correlation between estimated body fat or hours per day of exercise and the regularity of menses, duration of flow, or dysmenorrhea. With the exception of gymnastics and dancing, sports participation had little or no impact on menstrual patterns. Follow up questionnaires and menstrual calendars were obtained from 87 girls eight to fifteen months after the initial questionnaires. All girls whose cycles had changed from regular to irregular were boarding students, confirming previous anecdotal reports that separation from home may be a significant stress for adolescents.

Oligomenorrhea in adolescent girls

Forty-two patients ages 15 to 20 years (average 17.3 years) were evaluated for oligomenorrhea. Group I consisted of 19 patients with evidence of androgen excess (hirsutism, clitoromegaly, acne); and Group II included 23 patients without evidence of androgen excess. Sixteen of the 19 patients in Group I had elevated serum LH and normal FSH values. Serum total testosterone concentration was elevated in 12 patients and free T was elevated in one additional patient. In nine patients urinary 17KS excretion was elevated and dexamethasone suppressible. For the purpose of treatment, patients in Group I were divided into three subgroups: IA, polycystic ovary syndrome--12 patients; IB, adrenal block--two patients; IC, combined adrenal and ovarian hyperandrogenism--five patients. Among the 23 Group II patients, four had persistently elevated serum LH and normal FSH values, suggesting PCO; three had menopausal levels of LA and FSH; one had hyperprolactinemia and a depressed floor of the pituitary sella; and the remaining 15 patients had low to normal serum levels of LH and FSH, consistent with hypothalamic suppression. Guidelines for the diagnosis and treatment of adolescents with oligomenorrhea are discussed on the basis of these findings.

Contraceptive compliance with a triphasic and a monophasic norethindrone-containing oral contraceptive pill in a private adolescent practice

Study Objective: This study was undertaken to assess the impact of a monophasic and triphasic norethin-drone-containing oral contraceptive pill on reported side effects and compliance. Design: Adolescents initiating oral contraceptive use were studied at baseline, 3 months and 12 months, to determine compliance and side effects associated with the use of two oral contraceptive pills. Setting: A suburban private practice of adolescent medicine. Participants: Ninety-nine sexually active adolescent and young adult women were sequentially entered into the study (49 initiating a monophasic pill and 50 a triphasic pill). Outcome Measurements: Compliance with oral contraceptive use at 3 and 12 months was determined for adolescents and young adult women initiating the use of two oral contraceptive pills. Demographic data, sexual history, career goals, and concerns about use were collected before use. Compliance and side effects experienced were determined at 3 and 12 months. Results: There was no significant difference in compliance in the use of the two oral contraceptives at 3 and 12 months of follow-up. At 3 months, there was no difference in reported side effects, but at 12 months, patients taking the triphasic norethindrone pill were more likely to experience breakthrough bleeding than those taking the monophasic pill ( p = 0.001) and to change pills. Despite the common fear among adolescents of weight gain associated with oral contraceptive pill use, mean weight change at 3 months was not different between the two pills and was 0.59 and 0.55 kg for the monophasic and triphasic pill at 3 months and 1.00 kg and 1.24 kg for the monophasic and triphasic pills at 12 months. “Perceived” rather than actual weight gain led to discontinuation of the pill. Conclusion: Adolescents experienced more side effects on the triphasic than the monophasic norethindrone-containing pill but compliance was the same. Weight issues and breakthrough bleeding need to be addressed in suburban practices.

Regional Cerebral Blood Flow Differences During High-Caloric Food Challenge in Patients with Anorexia Nervosa Versus Normal Controls |[bull]| 9

Previous neuroimaging studies have employed symptom provocation paradigms to examine the functional neuroanatomic correlates of emotions or behaviors that characterize particular psychiatric disorders. This study was designed to determine areas of differential brain activity associated with the hallmark food aversion of anorexia nervosa (AN). We hypothesized that this feature of AN would be associated with dysfunction within the paralimbic system. The tracer, oxygen 15-labeled carbon dioxide, was used to make positron emission tomographic measurements of regional cerebral blood flow (rCBF). We compared 8 young women with AN to 8 medically/psychiatrically healthy female control subjects during both a neutral and provoked state. Presentation of standardized neutral, low-caloric food stimuli (apple, lettuce) was followed by viewing of provocative, high-caloric food stimuli (cake, bagel + cream cheese). Heart rate was monitored by pulse oximetry and subjects completed emotional state analog scales after each scan. Stereotactic transformation and statistical parametric mapping techniques were used to determine locations of significant activation; a statistical threshold of p=0.001 (z=3.09) was used for analysis of imaging data. Provocative food stimuli produced a significant desire to eat in controls (p=0.01), whereas in the AN group, identical stimuli produced significant disgust (p=0.008) and other negative emotions. A significant heart rate increase (p=0.023) was noted after exposure to provocative stimuli in AN subjects, but not in controls. Planned contrasts(rCBF for provoked vs. neutral conditions) demonstrated a significant decrease in rCBF within the left anterior temporal cortex in controls only. Within the AN group alone, significantly decreased rCBF was seen in the right somatosensory cortex in an area controlling sensory function of the mouth. These results implicate left anterior temporal cortex, a component of the paralimbic system, in the mediation of normal appetitive function and as an area that appears to be differentially activated in AN. Interestingly, subjects with AN had decreased activity in a brain region mediating oral sensation, accompanying their reported experience of high-caloric food aversion.

Estrogen deficiency in adolescents and young adults: Impact on bone mineral content and effects of estrogen replacement therapy

Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied, we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures (bone density, bone mineral content, and bone width) and the response to estrogen therapy. Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine, despite estrogen replacement. Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age, increased body mass index, spontaneous pubertal development, lack of radiation therapy, and lower serum osteocalcin. Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius, a slight improvement in bone density at the distal one-tenth of the radius, and an encouraging, but marginal, improvement in the z score (standard deviation from the mean) of bone mineral content at the distal onetenth. The z scores for cortical bone width and bone density decreased, suggesting a possible relative worsening over time. In untreated estrogen-deficient girls, bone mineral content and bone density decreased (but not significantly); the z score of cortical bone width showed a significant decrease. Using dual-photon absorptiometry, a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls. Estrogen/ progestin therapy did not result in changes in serum levels of lipids and antithrombin HI, weight, or blood pressure. This study suggests that because most adolescent/young adult patients with estrogen deficiency may not achieve normal bone density with current therapy, earlier and more aggressive intervention may be necessary.

Endocrinologic Sequelae of Anorexia Nervosa

Anorexia nervosa (AN) is a severe psychiatric and medical condition once described as the “relentless pursuit of thinness.” Eighty-five percent of patients with AN present between the ages of 13 and 20 years during a critical period for growth, pubertal development, and maximal bone accretion that culminates in peak bone mass. The disorder can result in a compromise in each of these important endocrinologic events, with lifelong sequelae. Recent trends demonstrate an earlier age of onset of AN, and it is recognized that onset at a younger age is associated with poorer growth and bone health outcomes. Patients with AN also have a characteristic clinical picture of endocrine dysfunction, including amenorrhea, abnormal temperature regulation, elevated growth hormone (GH) levels, hypercortisolemia, and abnormal eating suggestive of hypothalamic or pituitary dysfunction. Therefore, endocrine function has been studied extensively in these patients. The multiple endocrine abnormalities appear to represent an adaptation to the starvation state.