Amy D. DiVasta

The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa.

Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented.

Gynecomastia in adolescents

Purpose of review Gynecomastia is a common finding in adolescent men. The primary care provider should feel equipped to thoroughly evaluate this condition and to differentiate physiologic from pathologic breast enlargement. The present review focuses on the epidemiology, pathogenesis, evaluation, and treatment of gynecomastia during adolescence. Recent findings While gynecomastia has long been attributed to an imbalance between estrogen and androgen concentrations, recent literature has begun to illuminate other potential mechanisms for breast development in adolescent men. Increased leptin levels, as well as human chorionic gonadotropin and luteinizing hormone receptors on male breast tissue, may play a role. Newer treatment strategies, such as the antiestrogen raloxifene, have shown promising results; however, further studies are needed to determine long-term efficacy. As a result of the limited pharmaceutical treatment options, many more adolescents are seeking surgical intervention. Summary Gynecomastia is frequently encountered in the primary care setting. During adolescence, male breast enlargement is most often benign and rarely represents a pathologic mechanism. Careful attention should be paid to both the breast and testicular examination. A detailed history should include an inquiry regarding the use of illicit substances, anabolic–androgenic steroids, herbal products, and medications. The impact of gynecomastia on the adolescents mental health should be assessed. A workup for pathologic causes is rarely required. Reassurance remains the standard of care for physiologic gynecomastia.

Does hormone replacement normalize bone geometry in adolescents with anorexia nervosa

Young women with anorexia nervosa (AN) have reduced secretion of dehydroepiandrosterone (DHEA) and estrogen contributing to skeletal deficits. In this randomized, placebo‐controlled trial, we investigated the effects of oral DHEA + combined oral contraceptive (COC) versus placebo on changes in bone geometry in young women with AN. Eighty women with AN, aged 13 to 27 years, received a random, double‐blinded assignment to micronized DHEA (50 mg/day) + COC (20 µg ethinyl estradiol/0.1 mg levonorgestrel) or placebo for 18 months. Measurements of areal bone mineral density (aBMD) at the total hip were obtained by dual‐energy X‐ray absorptiometry at 0, 6, 12, and 18 months. We used the Hip Structural Analysis (HSA) program to determine BMD, cross‐sectional area (CSA), and section modulus at the femoral neck and shaft. Each measurement was expressed as a percentage of the age‐, height‐, and lean mass‐specific mean from an independent sample of healthy adolescent females. Over the 18 months, DHEA + COC led to stabilization in femoral shaft BMD (0.0 ± 0.5% of normal mean for age, height, and lean mass/year) compared with decreases in the placebo group (−1.1 ± 0.5% per year, p = 0.03). Similarly, CSA, section modulus, and cortical thickness improved with treatment. In young women with AN, adrenal and gonadal hormone replacement improved bone health and increased cross‐sectional geometry. Our results indicate that this combination treatment has a beneficial impact on surrogate measures of bone strength, and not only bone density, in young women with AN.

The Effect of Bed Rest on Bone Turnover in Young Women Hospitalized for Anorexia Nervosa: A Pilot Study

CONTEXT Malnourished adolescents with anorexia nervosa (AN) requiring medical hospitalization are at high risk for skeletal insults. Even short-term bed rest may further disrupt normal patterns of bone turnover. OBJECTIVE The objective of the study was to determine the effect of relative immobilization on bone turnover in adolescents hospitalized for AN. DESIGN This was a short-term observational study. SETTING The study was conducted at a tertiary care pediatric hospital. STUDY PARTICIPANTS Twenty-eight adolescents with AN, aged 13-21 yr with a mean body mass index of 15.9 +/- 1.8 kg/m(2), were enrolled prospectively on admission. INTERVENTION As per standard care, all subjects were placed on bed rest and graded nutritional therapy. MAIN OUTCOME MEASURE Markers of bone formation (bone specific alkaline phosphatase), turnover (osteocalcin), and bone resorption (urinary N-telopeptides NTx) were measured. RESULTS During the 5 d of hospitalization, serum osteocalcin increased by 0.24 +/- 0.1 ng/ml . d (P = 0.02). Urine N-telopeptides reached a nadir on d 3, declining -6.9 +/- 2.8 nm bone collagen equivalent per millimole creatinine (P = 0.01) but returned to baseline by d 5 (P > 0.05). Bone-specific alkaline phosphatase exhibited a decline that was strongly age dependent, being highly significant for younger subjects only [age 14 yr: -0.42 +/- 0.11 (P = 0.0002); age 18 yr: -0.03 +/- 0.08 (P = 0.68)]. Age had no effect on other outcome measures. CONCLUSION Limitation of physical activity during hospitalization for patients with AN is associated with suppressed bone formation and resorption and an imbalance of bone turnover. Future interventional studies involving mechanical stimulation and/or weight-bearing activity are needed to determine whether medical protocols prescribing strict bed rest are appropriate.

Prevalence and Predictors of Abnormal Liver Enzymes in Young Women with Anorexia Nervosa

OBJECTIVE To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN). STUDY DESIGN In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables. RESULTS Elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = -0.27 to -0.30, P < .049) and percentage body fat (r = -0.36 to -0.47, P < .007) but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs 18.0 U/L, P = .01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, P = .04). CONCLUSIONS Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine whether these liver enzyme elevations signify unrecognized, clinically relevant liver disease.

Bone cross-sectional geometry in adolescents and young women with anorexia nervosa: a hip structural analysis study.

IntroductionBetter characterization of bone geometry in adolescents with anorexia nervosa (AN) may improve understanding of skeletal deficits in this population. Our objective was to determine whether hip cross-sectional geometry and bone strength were altered in adolescents with AN.MethodsMeasurements of the left total proximal femur and body composition were obtained in 85 adolescents with AN and 61 healthy controls by dual X-ray absorptiometry. The Hip Structural Analysis (HSA) program was used to determine aBMD, cross-sectional area (CSA), and section modulus (Z) at the femoral neck and shaft. Strength indices were calculated and corrected for lean mass.ResultsFemoral neck and shaft aBMD were lower in AN patients than healthy controls (−36% and −29%, p < 0.001). In both regions, bone CSA and Z were lower in AN sufferers (−11 to −35%, p < 0.001). While lean body mass correlated with HSA variables (r = 0.48 to 0.58, p < 0.001), body fat did not. AN sufferers had lower indices of both whole bone strength (−40%, p < 0.001) and relative bone strength (−36%, p < 0.001) than controls.ConclusionsAnorexia nervosa sufferers had decreased resistance to axial (CSA) and bending loads (Z) compared with healthy controls. Differences in strength properties were significant even when adjusted for lean mass, suggesting that not only decreased mechanical loading, but also known metabolic differences are likely responsible for deficits in bone strength in these patients.

Clinical Variability in Approaches to Polycystic Ovary Syndrome

STUDY OBJECTIVE The objective of this study was to evaluate methods of initial diagnosis and management of polycystic ovary syndrome (PCOS) among members of the North American Society for Pediatric and Adolescent Gynecology (NASPAG) to assess the degree of practice heterogeneity among specialist providers of adolescent care. DESIGN Cross-sectional, anonymous, internet survey PARTICIPANTS NASPAG membership (N = 326; Respondents = 127 (39%)) RESULTS Percentage of respondents who incorporated specific tests at initial diagnosis was highly variable ranging from 87% (thyroid stimulating hormone) to 17% (sex hormone binding globulin). Oral contraceptives and diet modification/exercise were the most common therapies recommended by 98% and 90% of respondents respectively. CONCLUSION Considerable practice heterogeneity was present with regards to diagnostic testing for suspected PCOS. Recommendations for first-line therapy were more consistent. Future studies should clarify the clinical utility of specific diagnostic tests for adolescents, such that selection of diagnostic testing is evidence based.

Hormone replacement therapy for the adolescent patient.

Pubertal induction and hormone replacement therapy (HRT) during adolescence are conducted with the aim of closely mirroring the pubertal changes that occur in children with a normal hypothalamic‐pituitary‐ovarian axis. The challenge for the clinician is to determine the most appropriate form, dosing, and duration of replacement therapy to achieve that goal in an individual patient. While the optimal regimen remains unclear and data in adolescents are limited, this review presents the evidence available to clinicians as they care for adolescent girls and young women. Both the goals and phases of HRT are reviewed, and commonly used medication regimens are presented. Both the benefits and risks associated with various methods of HRT are also discussed, as are special issues of concern regarding adolescent HRT, including eating disorders and bone health.

The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis.

Purpose of review Endometriosis is increasingly being recognized and diagnosed in adolescents. As a result of this earlier diagnosis, treatment with agents like gonadotropin releasing hormone agonist (GnRHa) begins earlier and may last longer. Long-term effects of GnRHa treatment for endometriosis are of concern when treating adolescents. Recent findings GnRHas are used for adolescents with surgically confirmed endometriosis. GnRHa treatment is effective for pain reduction, but is associated with menopausal symptoms and decreases in bone density. Different regimens of hormonal add-back therapy have been studied in adults to attempt to prevent these side-effects. Summary GnRHa therapy is a highly effective, nonsurgical treatment option for many adolescents with endometriosis, but is accompanied by side-effects of bone loss and menopausal symptoms. Side-effects may be decreased by introducing appropriate add-back therapy. Monitoring of bone density by DXA is recommended for prolonged use of GnRHa in adolescents.

Expression of androgen, estrogen, progesterone, and growth hormone receptors in vascular malformations.

Background: Vascular malformations frequently enlarge during adolescence, suggesting that hormones may be involved. The purpose of this study was to determine whether pubertal hormone receptors are present in vascular malformations and whether they differ from normal tissue. Methods: Tissue specimens (arteriovenous malformation, lymphatic malformation, and venous malformation) were prospectively collected from patients undergoing resection. Immunohistochemistry was used to determine the presence of androgen, estrogen, progesterone, and growth hormone receptors. The effects of age, sex, location, and malformation type on receptor expression were analyzed. Age-, sex-, and location-matched normal tissues served as controls. Results: Forty-five vascular malformation specimens were collected: arteriovenous malformation (n = 11), lymphatic malformation (n = 20), and venous malformation (n = 14). Growth hormone receptor expression was increased in arteriovenous malformation (72.7 percent), lymphatic malformation (65.0 percent), and venous malformation (57.1 percent) tissues compared with controls (25.8 percent) (p < 0.05). Growth hormone receptor was present primarily in the endothelium/perivasculature of malformations (93.1 percent), whereas in normal tissue growth hormone receptor was located only in the stroma (p < 0.0001). Neither age, nor sex, nor location influenced receptor expression (p = 0.9). No differences in androgen receptor, estrogen receptor, and progesterone receptor staining were found between malformations and control samples (p = 0.7). Conclusions: Growth hormone receptor is overexpressed and principally located in the vessels of vascular malformations. Growth hormone might contribute to the expansion of vascular malformations.