Phthalate exposure and pubertal development in a longitudinal study of US girls.

STUDY QUESTION: Does phthalate exposure during early childhood alter the timing of pubertal development in girls? SUMMARY ANSWER: Urinary concentrations of high-molecular weight phthalate (high-MWP) metabolites are associated with later pubarche. WHAT IS KNOWN ALREADY: Phthalates are anti-androgenic environmental agents known to alter early development, with possible effects on pubertal onset. STUDY DESIGN, SIZE, AND DURATION: This multi-ethnic study included 1239 girls from New York City, greater Cincinnati, and the San Francisco Bay Area who were 6-8 years old at enrollment (2004-2007) and who were followed until 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Phthalate metabolites were measured in urine collected at enrollment from 1170 girls; concentrations ranged from <1 to >10,000 µg/l. Breast and pubic hair stages and body size were assessed one to two times annually to determine the age at transition from stage 1 to 2 for breast and pubic hair development. Associations between exposures and pubertal ages were estimated using Cox proportional hazard ratios (HR) with 95% confidence intervals (CI) and survival analyses. Associations were examined with respect to age-specific body mass-index percentile, one of the strongest predictors of pubertal onset. MAIN RESULTS AND THE ROLE OF CHANCE: Urinary concentrations of high-MWP including di(2-ethylhexyl) phthalate (ΣDEHP) metabolites were associated with later pubic hair development during 7 years of observation. The relationship was linear and was stronger among normal-weight girls. Among normal-weight girls, age at pubic hair stage 2 (PH2) was 9.5 months older for girls in the fifth compared with the first quintile of urinary ΣDEHP (medians: 510 and 59 µg/g creatinine, respectively; adjusted HR 0.70, CI 0.53-0.93, P-trend 0.005. Age at first breast development was older for fifth quintile of mono-benzyl phthalate versus first (HR 0.83, CI 0.68-1.02; P-trend 0.018). No associations were observed between low-molecular weight phthalate urinary metabolite concentrations and age at pubertal transition in adjusted analyses. LIMITATIONS, REASONS FOR CAUTION: While there is evidence that phthalate exposures are fairly consistent over time, the exposure measure in this study may not reflect an earlier, more susceptible window of exposure. We investigated alternative explanations that might arise from exposure misclassification or confounding. WIDER IMPLICATIONS OF THE FINDINGS: Phthalates are widespread, hormonally active pollutants that may alter pubertal timing. Whether exposures delay or accelerate pubertal development may depend on age at exposure as well as other factors such as obesity and exposures earlier in life. Whether exposures act independently or as part of real life mixtures may also change their effects on maturation from birth through childhood. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by the US National Institutes of Health, Environmental Protection Agency, New York State Empire Clinical Research Investigator Program and the Avon Foundation. L.H.K. is employed by Kaiser Permanente. The remaining authors declare they have no actual or potential competing financial interests.

Mechanism of cadmium-mediated inhibition of Msh2-Msh6 function in DNA mismatch repair.

The observation that Cadmium (Cd(2+)) inhibits Msh2-Msh6, which is responsible for identifying base pair mismatches and other discrepancies in DNA, has led to the proposal that selective targeting of this protein and consequent suppression of DNA repair or apoptosis promote the carcinogenic effects of the heavy metal toxin. It has been suggested that Cd(2+) binding to specific sites on Msh2-Msh6 blocks its DNA binding and ATPase activities. To investigate the mechanism of inhibition, we measured Cd(2+) binding to Msh2-Msh6, directly and by monitoring changes in protein structure and enzymatic activity. Global fitting of the data to a multiligand binding model revealed that binding of about 100 Cd(2+) ions per Msh2-Msh6 results in its inactivation. This finding indicates that the inhibitory effect of Cd(2+) occurs via a nonspecific mechanism. Cd(2+) and Msh2-Msh6 interactions involve cysteine sulfhydryl groups, and the high Cd(2+):Msh2-Msh6 ratio implicates other ligands such as histidine, aspartate, glutamate, and the peptide backbone as well. Our study also shows that cadmium inactivates several unrelated enzymes similarly, consistent with a nonspecific mechanism of inhibition. Targeting of a variety of proteins, including Msh2-Msh6, in this generic manner would explain the marked broad-spectrum impact of Cd(2+) on biological processes. We propose that the presence of multiple nonspecific Cd(2+) binding sites on proteins and their propensity to change conformation on interaction with Cd(2+) are critical determinants of the susceptibility of corresponding biological systems to cadmium toxicity.

Perfluorooctanoate and changes in anthropometric parameters with age in young girls in the Greater Cincinnati and San Francisco Bay Area.

METHODS: We conducted a study of per- and polyfluoroalkyl substance biomarkers, including PFOA, in girls from Greater Cincinnati (CIN, N = 353) and the San Francisco Bay Area (SFBA, N = 351). PFOA was measured in the baseline serum sample collected in 2004-2007 of 704 girls at age 6-8 years. Mixed effects models were used to derive the effect of PFOA on BMI, waist-to-height and waist-to-hip ratios over increasing age in this longitudinal cohort. RESULTS: Median PFOA serum concentrations were 7.3 (CIN) and 5.8 (SFBA) ng/mL, above the U.S. population median for children 12-19 years in 2005-2006 (3.8 ng/mL). Log-transformed serum PFOA had a strong inverse association with BMIz in the CIN girls (p = 0.0002) and the combined two-site data (p = 0.0008); the joint inverse effect of PFOA and Age*PFOA weakened at age at 10-11 years. However, in the SFBA group alone, the relationship was not significant (p = 0.1641) with no evidence of changing effect with age. The effect of PFOA on waist:height ratio was similar to BMIz at both sites, but we did not find a significant effect of PFOA on waist:hip ratio in either the CIN or SFBA girls. CONCLUSIONS: PFOA is associated with decreased BMI and waist:height ratio in young girls, but the strength of the relationship decreases with age. Site heterogeneity may be due to greater early life exposure in Cincinnati. DISCLAIMER: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.

Romantic, sexual, and sexual risk behaviours of adolescent females with severe obesity.

BACKGROUND: There is an increasing adolescent population with severe obesity with impairments in social and romantic relationships that are seeking clinical weight management, including weight loss surgery (WLS). OBJECTIVE: To document romantic, sexual and sexual risk behaviours in a clinical sample of adolescent females with severe obesity (BMI > 40 kg/m2 ) compared to those of healthy weight (HW). METHODS: This multi-site study-an ancillary to a prospective longitudinal observational study documenting health in adolescents having WLS-presents pre-operative/baseline data from 108 females undergoing WLS, 68 severely obese seeking lifestyle intervention and 118 of HW. Romantic and sexual risk behaviour and birth control information sources were assessed using the Sexual Activities and Attitudes Questionnaire (SAAQ). RESULTS: Severely obese females reported engaging in fewer romantic and sexual behaviours compared to HW. Similar to HW, a subgroup (25%) of severely females were engaging in higher rates of sexual risk behaviours and reported pregnancies and sexually transmitted infections (STIs). A considerable number (28-44%) reported receiving no birth control information from physicians. CONCLUSIONS: Discussion topics with the adolescent patient should extend beyond reproductive health needs (e.g. contraception, unintended pregnancies) to include guidance around navigating romantic and sexual health behaviours that are precursors to these outcomes.

Longitudinal correlates of change in blood pressure in adolescent girls.

The objective of this study was to assess the longitudinal changes in blood pressure in black and white adolescent girls and evaluate potential determinants of changes in blood pressure, including sexual maturation and body size. A total of 1213 black and 1166 white girls, ages 9 or 10 years at study entry, were followed up through age 14 with annual measurements of height, weight, skinfold thickness, stage of sexual maturation, systolic and diastolic blood pressures, and other cardiovascular risk factors. Average blood pressures in black girls were generally 1 to 2 mm Hg higher than in white girls of similar age over the course of the study. Age, race, stage of sexual maturation, height, and body mass index (kg/m2) were all significant univariate predictors of systolic and diastolic blood pressures in longitudinal regression analyses. Black girls had a significantly smaller increase in blood pressure for a given increase in body mass index compared with white girls. The predicted increases in blood pressure per unit increase in body mass index (mm Hg per kg/m2) were as follows: systolic, 0.65+/-0.04 in whites and 0.52+/-0.04 in blacks (P<.001); diastolic fourth Korotkoff phase, 0.31+/-0.04 in whites and 0.15+/-0.03 in blacks (P<.001); and diastolic fifth Korotkoff phase, 0.31+/-0.05 in whites and 0.16+/-0.04 in blacks (P<.001). Understanding of the determinants of the racial differences in blood pressure could provide the rationale for future interventions to reduce the excess cardiovascular mortality in black compared with white women.

The hypermobility syndrome.

The hypermobility syndrome has been recognized as a definitive diagnostic entity among children referred to a Pediatric Arthritis Clinic with musculoskeletal complaints. The diagnosis of hypermobility was made by the ability of the patients to perform at least three of the following maneuvers: (1) extension of the wrists and metacarpal phalanges so that the fingers are parallel to the dorsum of the forearm; (2) passive apposition of thumbs to the flexor aspect of the forearm; (3) hyperextension of elbows (greater than or equal to 10 degrees); (4) hyperextension of knees (greater than or equal to 10 degrees); (5) flexion of trunk with knees extended so palms rest on the floor. Of 262 patients, 15 (5.7%) referred to an arthritis clinic between January 1979 and July 1981 were subsequently determined to have hypermobility as the basis for their rheumatic complaints. Three of these 15 had concomitant juvenile arthritis. The presenting complaint of pain was most often localized to the knees, hands, and fingers. Arthritis and elevated ESRs were not seen except in the three patients who had concomitant juvenile arthritis. All patients responded to physical therapy and nonsteroidal analgesic anti-inflammatory drugs. This is an entity not sufficiently well recognized as a source of musculoskeletal complaints in the United States. It will usually respond well to reassurance and symptomatic therapy.

A comparison of diagnostic methods in adolescent girls with and without symptoms of Chlamydia urogenital infection.

OBJECTIVE: To evaluate the clinical utility of various diagnostic tests, two enzyme immunoassays and a chemiluminescent DNA probe were compared with cell culture (with monoclonal antibody confirmation) for the diagnosis of endocervical Chlamydia trachomatis infection. DESIGN: The clinical performance of four diagnostic methods for Chlamydia trachomatis urogenital infections were compared, using specimens generated from consecutive pelvic examinations. SETTING: Subjects were recruited from an urban adolescent clinic that provides primary and referral care. PARTICIPANTS: A total of 479 adolescent female subjects were enrolled. The order of sample collection was randomized. Subjects were stratified according to whether they were asymptomatic (n = 228) or symptomatic (n = 251). MEASUREMENTS AND RESULTS: Discrepant analysis was performed when culture was negative and nonculture technique was positive. The subject was considered to have chlamydia if culture was positive, or if one or more nonculture techniques, with that test's confirmatory assay, were positive (consensus-positive). Prevalence of chlamydia was 11.0% in the asymptomatic, and 20.7% in the symptomatic, group. Overall, 32.5% of the infected subjects were asymptomatic. Sensitivity of diagnostic methods varied from 52% to 80% in the asymptomatic subjects, compared with 65% to 81% in symptomatic subjects. Culture sensitivity was 75% to 80%. The specificities of all tests were 96% or greater. Accuracy of nonculture methods varied from 89.5% (DNA probe, symptomatic subjects) to 96.9% (enzyme immunoassay asymptomatic subjects). CONCLUSIONS: There are significant differences in symptomatic subjects when evaluating accuracy of test outcome, using a consensus-positive criterion. Asymptomatic infections account for nearly one third of adolescent females infected with chlamydia. The prevalence of chlamydia urogenital infections are underestimated by any single diagnostic test, particularly in the asymptomatic patient.

Differential classification of blood pressure by fourth and fifth Korotkoff phases in school-aged girls. The National Heart, Lung, and Blood Institute Growth and Health Study.

The use of the onset of the fourth (K4) or fifth (K5) Korotkoff phase to determine diastolic blood pressure in children has been controversial; most recently, the Second Task Force recommended the use of K4 for children up to age 13 years and K5 for children age 13 and above. We performed a cross-sectional analysis of 1,155 nine-year old (53% white and 47% black) and 1,224 ten-year old girls (45% white and 55% black) in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). The mean blood pressures for the first, fourth, and fifth Korotkoff phases were 100.1 (+/- 8.9) mm Hg, 66.6 (+/- 9.8) mm Hg, and 56.8 (+/- 11.8) mm Hg for nine-year-olds and 102.8 (+/- 9.0) mm Hg, 68.1 (+/- 10.1) mm Hg, and 58.1 (+/- 11.9) mm Hg for ten-year-olds. The mean difference between K4 and K5 was 9.9 (+/- 6.4) mm Hg. The correlation between K1 and K4 was 0.45, between K1 and K5 was 0.34, and between K4 and K5 was 0.84. Elevation of blood pressure was defined at or above the 95th percentile based on the NGHS distribution for K1, K4, or K5; the relative risk of having an elevated K1 was 10.1 if K4 was elevated and 5.9 if K5 was elevated. Of the 159 subjects potentially classified with elevated diastolic pressure, 95 subjects (60%) would be classified differently depending on whether K4 or K5 was used to define elevated diastolic blood pressure. The choice of the onset of the fourth or fifth Korotkoff phase for determining diastolic blood pressure in children may have important implications for which individuals are classified as having hypertension.

The conjoint trait of low high-density lipoprotein cholesterol and high triglycerides in adolescent black and white males.

To evaluate the interrelationships among body composition, blood pressure, and lipid phenotypes in adolescent black and white boys, we assessed racial distributions of lipids, blood pressure, and obesity and their joint occurrence in black and white boys aged 10 to 15 years. Subjects were recruited from Cincinnati (OH) schools. Because the differences in high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) are the most profound coronary heart disease (CHD) risk factor differences between black and white males, we assigned subjects to one of four low-HDL-C and high-TG categories (normal and increased risk) using the age/race-specific 25th (HDL-C) and 75th (TG) percentiles. We then assessed racial distributions of lipids, blood pressure, and obesity by these phenotypes. Age differences between the black and white participants were significant, with the former about 3 months younger (P=.03), but black boys were more mature and were significantly taller and heavier and had a greater body mass index ([BMI] weight in kilograms divided by height in centimeters squared). Differences in the sum of the triceps, subscapular, and suprailiac skinfolds were not significant. Blacks had significantly higher HDL-C, lower TG, and higher diastolic blood pressure (DBP), but differences in systolic blood pressure (SBP) were not significant. In both racial groups, the body composition measures were significantly correlated with HDL-C, TG, and blood pressure levels; the correlations between HDL-C and both weight and BMI were significantly stronger in white boys. The proportion of boys of each race with low HDL-C and high TG was similar by design. In both racial groups, subjects with the conjoint trait had a significantly greater BMI, triceps skinfold, and sum of skinfolds than subjects in the other phenotypic groups. For white boys, participants with the conjoint trait had the highest SBP and DBP; differences in SBP were significant for comparisons to the normal- and high-TG group alone, and differences in DBP were significant for the comparison between normal and low HDL-C alone. For black boys, subjects with both normal HDL-C and TG had significantly lower SBP than boys with either the conjoint trait or high TG alone; none of the group differences in DBP were significant. Black had significantly less dense LDL (more LDL-C per apolipoprotein [apo] B). In each racial group, boys with the conjoint trait had the most dense LDL, significantly more dense than in any of the other phenotypes in black boys and significantly more dense than in boys with low HDL-C alone and normal boys in the white group. In both racial groups, the occurrence of no risk factors (>75th percentile TG, BMI, SBP, and DBP or <25th percentile HDL-C) and three or more risk factors was greater than expected by chance alone, and the occurrence of exactly one risk factor and two factors was less. When examined by phenotypic groups within race, boys in each racial group with the normal phenotype had a greater than expected percentage with no risk factors, and white boys with the conjoint trait were more likely to have a marked increase in multiple risk factors. Possible mechanisms for this clustering of risk factors and for the racial differences in the patterns are discussed.

Estradiol and testosterone effects on lipids in black and white boys aged 10 to 15 years.

Previous studies of lipids in adolescent males have shown greater increases in triglycerides and decreases in high-density lipoprotein cholesterol (HDL-C) in white boys compared with black boys, significant correlations between sex hormones and lipids, and complex body mass index (BMI) hormone-lipid associations. Within this frame of reference, we assessed race, BMI, and sex hormones as predictors of lipid parameters in 536 black and white boys recruited from area schools. Black boys were more advanced in puberty than white boys. After adjusting for pubertal stage, estradiol (E2) levels were higher in black boys but free testosterone (T) levels did not differ. Age, pubertal stage, race, BMI, free T, and E2 were entered as explanatory variables for lipids in backward stepwise regression analyses. The BMI and race were retained in every model. Black boys had lower triglycerides and apolipoprotein B (apo B) and higher HDL-C. E2 was inversely associated with total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), apo B, and the LDL-C/HDL-C ratio. Free T was inversely associated with HDL-C and positively associated with apo B. Given the increases in free T and E2 during adolescence and the association of these hormones with both atherogenic and protective lipid parameters, racial differences in E2 could contribute to the more atherogenic lipid profile found in white boys after puberty.

Lipoprotein and apolipoprotein differences in black and white girls. The National Heart, Lung, and Blood Institute Growth and Health Study.

OBJECTIVE: To define racial differences in lipoprotein and apolipoprotein levels in girls aged 9 to 10 years. DESIGN: Baseline analysis of a prospective cohort study. SETTING: Three clinical sites. SUBJECTS: A total of 1871 black and white girls, aged 9 to 10 years, with complete maturation data (pubic hair and areolar development and menarche) and an 8-hour fast before blood draw. MAIN OUTCOME MEASURES: Anthropometric measures and serum lipid, lipoprotein, and apolipoprotein levels. RESULTS: All analyses were adjusted for maturational differences between blacks and whites (areolar or pubic hair development and menarche). The mean body mass index was marginally higher in black girls than in white girls (18.9 vs 18.3 kg/m2; P = .002), while the sum of skinfolds (34.5 vs 34.8 mm; P = .77) was equivalent. However, both body mass measures were skewed higher at the upper percentiles in black girls. The low-density lipoprotein cholesterol level was similar between black and white girls. Mean triglyceride values were higher in white girls than in black girls (0.92 vs 0.79 mmol/L [81 vs 70 mg/dL]; P < .001); however, these differences were most pronounced in the upper percentiles. Conversely, mean high-density lipoprotein cholesterol and apolipoprotein A-I levels were higher in black girls than in white girls (1.44 vs 1.37 mmol/L [56 vs 39 mg/dL] and 147 vs 138 mg/dL, respectively; both P < .001); and again the differences were most evident at the upper end of the distributions. CONCLUSIONS: Racial differences in the mean levels of triglycerides, high-density lipoprotein cholesterol, and body mass in girls in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) at age 9 to 10 years were predominantly the result of differences observed at the upper end of the distributions. The reported black-white differences for mean high-density and low-density lipoprotein cholesterol and triglyceride levels in adult women are comparable to NGHS results. Distributional characteristics of these risk factors as well as trends in lipids, lipoproteins, and apolipoproteins, will be evaluated in an ongoing longitudinal assessment that covers the full maturational period.

Acne vulgaris in early adolescent boys. Correlations with pubertal maturation and age.

To assess the prevalence and severity of acne vulgaris in young adolescent boys, we studied 219 black and 249 white boys in fifth through ninth grades in Cincinnati, Ohio. The mean age was 12.2 +/- 1.4 years, with a range of 9 to 15 years. Pubertal maturation was scored as Tanner pubic hair stages (PH I to V) and pubertal stages (PS I to IV) that included testicular volume assessment. Acne was scored by number of comedonal (open plus closed comedones) and inflammatory (papules plus pustules) lesions. Comedonal and inflammatory lesions were analyzed separately and evaluated both as numerical scores and as grades (1, less than or equal to 10 lesions; 2, 11 to 25 lesions; and 3, greater than or equal to 26 lesions). Grades 2 and 3 were considered clinically significant acne. Acne became progressively more severe with advancing maturity. Mean acne scores correlated better with PS and pubic hair than with age. Black subjects were more mature than white subjects. Black boys in PSI and II had significantly more comedones than white boys; white boys had significantly more inflammatory lesions at PS I and III. Clinically significant comedonal acne was already present in PS I and occurred in 100% of boys in PS IV. In contrast, no boys at PS I and only 50% at PS IV had significant inflammatory acne. Midfacial acne dominated. We concluded that acne prevalence and severity correlate well with advancing pubertal maturation in young adolescent boys. Comedonal acne was more frequent and severe than inflammatory disease. Awareness of the extent and severity of acne in preadolescents and young adolescents may ultimately provide rationale for early intervention and thus prevention of severe acne vulgaris.

Acne vulgaris in premenarchal girls. An early sign of puberty associated with rising levels of dehydroepiandrosterone.

BACKGROUND: This study examined the relationships of pubertal maturation and sex steroid hormones to the development of acne in young girls. Black (n = 317) and white (n = 306) premenarchal girls with a mean age of 9.97 +/- 0.62 years were evaluated for acne prevalence and severity, pubic hair and areolar maturation, and sex steroid hormone levels. RESULTS: Overall, 77.8% of the girls had some acne; of the whole group, 48.3% had only comedonal acne, 2.2% had only inflammatory acne, and 27.3% had both types. Although black girls matured at an earlier age than white girls, racial differences in acne were minimal when adjusted for pubertal maturation. Acne increased with advancing maturation; at Tanner pubic hair stages 1, 2, and 3, the prevalence of acne rose from 73.1% to 84.0% and to 90.6%, respectively. Acne lesion counts at seven facial locations revealed a predominance of midfacial acne on the middle aspect of the forehead, nose, and chin. Sex steroid hormone levels measured in 365 of the girls were found to increase significantly during maturation from prepuberty to early puberty. Testosterone-estrogen-binding globulin and the ratio of testosterone to estradiol decreased. In 118 prepubertal girls, estradiol, total and free testosterone, progesterone, testosterone to estradiol ratio, and testosterone-estrogen-binding globulin levels were no different whether in subjects with acne or without acne. However, the level of dehydroepiandrosterone sulfate, an androgen of adrenal origin, was significantly higher in prepubertal girls with acne. CONCLUSION: Acne, especially the comedonal type, can be the first sign of pubertal maturation in girls, even preceding pubic hair and areolar development. Concentration of dehydroepiandrosterone sulfate is significantly and specifically associated with the initiation of acne in young girls.

Genital human papillomavirus infection in adolescents.

Genital HPV infections are much more prevalent than previously believed. The most common clinical manifestation of HPV--the subclinical papillomavirus infection, or SPI--is missed on routine examination. No single diagnostic test is adequate in the assessment of HPV infections, and the more recent studies involving newer nucleic acid technologies have brought about a better understanding of the behavior of HPV. There are different oncogenic potentials regarding specific HPV DNA types. Other possible cofactors include age at diagnosis, method of contraception, and use of tobacco.

Surveying graduates of combined internal medicine-pediatrics residency programs.

Graduates of all U.S. combined internal medicine-pediatrics residency programs were surveyed in 1987 regarding a variety of demographic information about their residencies and current practices, the residency curricula they had followed for both specialties, and recommendations for modifications in training. The 71 responding graduates (from a total of 112) reported patient care as their major involvement (mean of 42.9 hours per week), with a majority (83%) seeing patients in both pediatric and adult age groups. Most were involved in primary care only (64%). The graduates reported that during both pediatrics and internal medicine training, they had had too many inpatient and intensive care rotations and too few elective and ambulatory rotations. The most important subspecialty rotations in internal medicine were considered to be cardiology, dermatology, and pulmonary medicine; and in pediatrics, infectious disease, cardiology, and adolescent medicine. The graduates recommended more outpatient subspecialty rotations, ambulatory rotations in medicine and pediatrics, and a combined medicine-pediatrics continuity clinic.

Drug treatment of nonviral sexually transmitted diseases: specific issues in adolescents.

Sexually transmitted diseases (STDs) are common and happen more frequently in younger patients. These adolescents have unique risks of acquiring infection because of developing psychosocial skills, biological factors and sociocultural barriers. The clinician must be adept at identifying and modifying these risks through knowledge of the adolescent stages of development and biology, with good history and examination skills that make teens comfortable during their evaluation, and with patient education and treatment. Whereas patient compliance and partner notification can be problematic in any population, teenagers may be more prone not to follow through on these issues. While compliance may notbe as important as previously thought, there is a dearth of studies of patient compliance and STD treatment in adolescents. Guidelines for the treatment of STDs were published by the Centers for Disease Control and Prevention (CDC) in 1998 and the Medical Society for the Study of Venereal Diseases in 1999. Most of the data obtained to formulate these guidelines were not necessarily adolescent specific and few studies, if any, have included adolescent patients since the CDC document was published. In the treatment of chlamydia, it appears that even with relative noncompliance with the 7-day regimen of doxycycline, it is as effective as single dose azithromycin. This has implications in cost control, important for centres with limited funds for treatment. While fluoroquinolone-resistant gonorrhoea has been reported for some time, the number of reports in the US is increasing, with a recent report of decreased susceptibility to azithromycin. As many studies have shown efficacy with single agent therapy with azithromycin in combined gonococcal and chlamydial infection, one must view these new resistance data with concern and give serious consideration to dual agent treatment, especially in the locale of the practitioner. Also, fluoroquinolone use is not advised in patients under the age of 18 years at present because of concerns of adverse effects on cartilage. While not much has changed from the 1998 guidelines for most of the other STDs, there seems to be a general trend in treating pelvic inflammatory disease (PID) on an outpatient basis if good follow-up is assured, even in the adolescent population. There is still debate on whether anaerobe coverage is needed in PID without tubo-ovarian abscess or other complications. One other update includes the use of daily metronidazole gel instead of twice daily usage in the treatment of bacterial vaginosis. With the lack of studies specific to adolescents, it is left up to the clinician to tailor the treatment of adolescents on the basis of current guidelines and patient preferences.

Experience with side effects and health risks associated with Norplant implant use in adolescents.

Levonorgestrel implants (Norplant) have been recommended as a contraceptive method for teenage women. Our experience suggests that the use of Norplant implants in adolescents is associated with bleeding irregularities and modest weight gain. There is no effect on condom use or STD acquisition. Despite the bleeding irregularities, we documented high continuation rates, suggesting that with appropriate pre-insertion counseling, Norplant implants can be a successful contraceptive method for adolescent women.

PIP: An analysis of the experiences of 72 US adolescents (mean age, 15.5 years) suggests that Norplant implants are an appropriate contraceptive method for this population. All study participants had the implants inserted at a hospital-based adolescent clinic at least 1 year before chart review. The continuation rate was 97% at 12 months and 86% at 24 months. At insertion, 60 adolescents (83%) reported regular menstrual periods. At the various follow-up intervals (e.g., 3, 6, and 12 months), 12-18% had regular periods, 12-16% were amenorrheic, and the remainder had bleeding that was irregular in length and/or interval. Mean weight gains of 3, 4.5, and 5.8 pounds were recorded at 3, 6, and 12 months, respectively; however, there was no consistent trend and a substantial number of young women lost weight during the study period. Finally, there was no clear trend of increase or decrease after Norplant insertion in either condom use or rates of infection with sexually transmitted diseases (STDs). Pre-insertion counseling for adolescent Norplant acceptors should include preparation for menstrual irregularities and encouragement of condom use to prevent STD acquisition.

Urinary leukocyte esterase screening for asymptomatic sexually transmitted disease in adolescent males.

The objective of this study was to evaluate the effectiveness of urinary leukocyte esterase on random urine specimens as a screening test for chlamydial and gonococcal urethral infections in asymptomatic males. Random urine specimens were obtained on 106 consecutive asymptomatic adolescent males during intake physical examination at a residential vocational training program. Results of urinary leukocyte esterase were compared to those of urethral cultures for Chlamydia trachomatis and Neisseria gonorrhoeae. Five subjects had positive chlamydia cultures, three subjects had positive gonococcal cultures, and one patient had positive cultures for both organisms. Sixteen subjects had leukocyte esterase tests reported as "trace" or greater. When compare to positive culture results for either Chlamydia or gonorrhea, urinary leukocyte esterase activity had a sensitivity of 78%, specificity of 91%, and positive predictive value of 44%. A random urine specimen for urinary leukocyte esterase activity is a cost-effective screening method for chlamydial and gonococcal urethral infections in asymptomatic adolescent males.

Effects of long term treatment with sertraline (Zoloft) simulating hypothyroidism in an adolescent.

A 16-year-old depressed adolescent, who had received sertraline treatment for the previous 18 months, developed insomnia, daytime somnolence and lack of energy. His thyroid function tests revealed low levels of total T4 with normal levels of free T4 and TSH, and a normal thyrotropin-releasing hormone (TRH) stimulation test. Discontinuing sertraline resulted in improved sleep and disappearance of daytime somnolence. Although daytime somnolence and low levels of total T4 can mimic hypothyroidism, in this case sertraline only displaced the bound-fraction of total T4 and was not associated with true hypothyroidism.

Depo-Provera in adolescents: effects of early second injection or prior oral contraception.

PURPOSE: To examine the effects of an early second injection or prior use of oral contraceptive pills (OCP) on side effects of Depo-Provera during the early months of use in adolescents. METHODS: Thirty-six girls, gynecologic age 4.2 +/- 0.3 years, and body mass index (BMI) 23.2 +/- 0.8, received the currently recommended injection of 150 mg every three months. Twenty-seven girls (gynecologic age 3.9 +/- 0.5 years, BMI 24.0 +/- 0.8) received the second injection six weeks after the first injection. Fifteen girls (gynecologic age 5.0 +/- 0.5, BMI 25.4 +/- 1.3) switched directly from an OCP to Depo-Provera. The patients were periodically assessed by their care providers. RESULTS: Early administration of the second injection of Depo-Provera did not alter the bleeding episodes, onset of bleeding, or total days of bleeding (14.3 +/- 3.7 vs. 17.1 +/- 4.0, p = 0.62) during the three months interval following injection, compared with the standard second injection interval. Moreover, an excessive BMI gain (BMI increase 0.99 +/- 0.22 vs. 0.40 +/- 0.14, p = 0.03) was observed in these girls. Girls who switched directly from OCP showed no difference in the rate of BMI gain when compared to those not previously on OCP (BMI increase 0.38 +/- 0.3). Bleeding duration of these girls, however, was markedly reduced; the total number of days of bleeding was 5.7 +/- 1.9 (p = 0.0003) during the first three month interval, and 5.7 +/- 2.3 (p = 0.019) during the three month period following the second injection. This reduction did not persist beyond the first six months. CONCLUSIONS: Early second Depo-Provera injection does not alter the experience of menstrual abnormalities, and predisposes to greater weight gain; OCP use prior to Depo-Provera results in a decrease in the duration of bleeding with no change in the weight gain rate.

PIP: The capability of an early second injection or prior use of oral contraceptives (OCs) to improve satisfaction and long-term continuation of Depo-Provera in adolescents was investigated in a clinical trial involving 78 females 12-20 years of age (average, 15.9 years) recruited from a hospital-based adolescent health clinic. 36 subjects received injection of 150 mg of Depo-Provera every three months (Group 1), 27 received the second injection after only six weeks (Group 2), and 15 switched directly from OCs to the standard Depo-Provera regimen (Group 3). There was no difference between Groups 1 and 2 in terms of duration or frequency of menstrual bleeding; however, prior OC users experienced a significant reduction in the duration and intensity of bleeding in the first six months of Depo-Provera use (when estrogen was still present in the women's systems). Overall, 64% of study subjects reported less dysmenorrhea while on Depo-Provera. A slightly greater change in body mass index was observed among girls in Group 2 than in Groups 1 and 3; moreover, 70% of those in the early injection group reported increased appetite and weight gain compared to 39% of those on the standard schedule. The most commonly reported side effects included initial pain and soreness at the injection site (27%), decreased libido (56%), mood changes (31%), depression (26%), frequent headache (25%), fatigue (24%), and increase in acne (15%); there were no significant differences by group. 17 adolescents (22%) discontinued Depo-Provera, generally after two injections and due to bleeding irregularities or weight gain. 87% of adolescents who were prior OC users, 52% of those on the regular schedule, and 39% of those who received an early injection stated they were very satisfied with Depo-Provera. These findings indicate that early second Depo-Provera injection offers no advantages; use of OCs immediately prior to Depo-Provera should be further investigated, however, given its potential to minimize bleeding problems.