Inadequate vitamin D status in adolescents with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate injectable contraceptive: a pilot study.

STUDY OBJECTIVE: To examine vitamin D and parathormone (PTH) levels in adolescents who experienced substantial bone mineral density (BMD) loss during depot medroxyprogesterone acetate (DMPA) use. DESIGN: A non-randomized, multi-center study, during which DMPA was administered every 12 weeks and evaluation of lumbar spine and hip BMD by dual-energy X-ray absorptiometry (DXA) was conducted every 6 months. A blood sample for vitamin D and PTH measurements was obtained from adolescents who experienced >5% BMD loss. Vitamin D deficiency was defined as 25-hydroxyvitamin D (25OHD) level of <20 ng/mL, insufficiency as 25OHD level of 20-30 ng/mL, and sufficiency as 25OHD level of >30 ng/mL. RESULTS: Evaluation of vitamin D and PTH was carried out in 15 participants who experienced BMD loss of > or = 5% during DMPA use. At initiation of DMPA, participants had mean (+SE) age 17+1 years, gynecologic age 61+4 months, and body mass index 24+1.5 kg/m2. Racial/ethnic distribution was: Caucasian--7 girls, Hispanic--4 girls, African-American--3 girls, and other--1 girl. Six participants had BMD loss of >5% after 2 DMPA injections, five after 3 injections, one after 5 injections, one after 8 injections, one after 10 injections, and one after 13 injections. Only one girl (7%) had sufficient vitamin D. The other participants had vitamin D insufficiency (50%) or deficiency (43%). Participants' mean (+SE) PTH was 22+4 pg/mL (reference range 7-53 pg/mL), and mean (+SE) 1,25-dihydroxyvitamin D was 56+5 pg/mL (reference range 22-67 pg/mL). CONCLUSIONS: Inadequate vitamin D status was evident among the majority of female adolescents who experienced a substantial BMD loss while using DMPA.

Comparison of clinical evaluation of genitourinary symptoms in female adolescents among primary care versus emergency department physicians.

OBJECTIVE: To compare clinical approaches to assessment and treatment of female adolescents with genitourinary symptoms among primary care and emergency department (ED) physicians. DESIGN: A chart review was performed of the evaluation and treatment of 472 patients presenting between July 1, 2005, and June 30, 2006. SETTING: Suburban and tertiary care EDs and primary care settings. PARTICIPANTS: Female patients age 13-21 years with genitourinary symptoms. INTERVENTIONS: None. OUTCOME MEASURES: Physician assessment of sexual history, performance of pelvic exam and sexually transmitted infection (STI) tests, empiric treatment of suspected STIs. RESULTS: Patients seen in primary care settings were more likely to be asked about sexual history, including contraceptive use, than patients in the ED (P<0.001). After adjustment for age and race, there was no statistically significant difference between the ED and primary care sites in performance of pelvic exams or gonorrhea and chlamydia tests. However, there was a higher likelihood that older adolescents would undergo pelvic exams (P=0.001), and STI testing (P=0.002) than younger patients. There was no significant difference in empiric treatment of patients with positive STI tests between ED and primary care sites or across the age spectrum. CONCLUSIONS: ED physicians should obtain sexual histories on patients with genitourinary symptoms. Both primary care and ED clinicians should consistently test for STIs in sexually active patients who have genitourinary symptoms. Physicians in both settings should have a low threshold for testing and empirically treating adolescents with symptoms or physical exam findings consistent with STIs.

An updated unified pharmacophore model of the benzodiazepine binding site on gamma-aminobutyric acid(a) receptors: correlation with comparative models.

A successful unified pharmacophore/receptor model which has guided the synthesis of subtype selective compounds is reviewed in light of recent developments both in ligand synthesis and structural studies of the binding site itself. The evaluation of experimental data in combination with a comparative model of the alpha1beta2gamma2 GABA(A) receptor leads to an orientation of the pharmacophore model within the Bz BS. Results not only are important for the rational design of selective ligands, but also for the identification and evaluation of possible roles which specific residues may have within the benzodiazepine binding pocket.

A role for the 2' residue in the second transmembrane helix of the GABA A receptor gamma2S subunit in channel conductance and gating.

GABA(A) receptors composed of alpha, beta and gamma subunits display a significantly higher single-channel conductance than receptors comprised of only alpha and beta subunits. The pore of GABA(A) receptors is lined by the second transmembrane region from each of its five subunits and includes conserved threonines at the 6', 10' and 13' positions. At the 2' position, however, a polar residue is present in the gamma subunit but not the alpha or beta subunits. As residues at the 2', 6' and 10' positions are exposed in the open channel and as such polar channel-lining residues may interact with permeant ions by substituting for water interactions, we compared both the single-channel conductance and the kinetic properties of wild-type alpha1beta1 and alpha1beta1gamma2S receptors with two mutant receptors, alphabetagamma(S2'A) and alphabetagamma(S2'V). We found that the single-channel conductance of both mutant alphabetagamma receptors was significantly decreased with respect to wild-type alphabetagamma, with the presence of the larger valine side chain having the greatest effect. However, the conductance of the mutant alphabetagamma receptors remained larger than wild-type alphabeta channels. This reduction in the conductance of mutant alphabetagamma receptors was observed at depolarized potentials only (E(Cl) = -1.8 mV), which revealed an asymmetry in the ion conduction pathway mediated by the gamma2' residue. The substitutions at the gamma2' serine residue also altered the gating properties of the channel in addition to the effects on the conductance with the open probability of the mutant channels being decreased while the mean open time increased. The data presented in this study show that residues at the 2' position in M2 of the gamma subunit affects both single-channel conductance and receptor kinetics.

Selections from current literature: Recent developments in human HIV-1 vaccine.

This article reviews recent changes in the design of HIV-I vaccine. The safety information for current vaccines has been established, and future ethical considerations are reviewed. Of recent significance, gp120 envelope vaccines are being combined with canarypox vectors in an effort to elicit a broad immune response. This will probably be the aim of future research for an ever-growing problem. A total of 10 143 AIDS cases have occurred in the USA in the year 2000.(1) The international burden is grimmer. For example, approximately 13% of South Africans between 20 and 64 years old are HIV positive. Predictions estimate this number to rise to almost 30% by 2010.(2) With many different HIV serotypes, a worldwide effective HIV vaccine is not in the near future.(3) However, the scientific community has bolstered its effort by strengthening resources and developing national and international collaboration groups focused in developing a safe and effective HIV vaccine.

Abortion in adolescence: a four-country comparison.

The purpose of this study was to conduct a comparison, using qualitative analytic methodology, of perceptions concerning abortion among health care providers and administrators, along with politicians and anti-abortion activists (total n = 75) in Great Britain, Sweden, The Netherlands, and the United States. In none of these countries was there consensus about abortion prior to legalization, and, in all countries, public discussion continues to be present. In general, after legalization of abortion has no longer made it a volatile issue European countries have refocused their energy into providing family planning services, education, and more straightforward access to abortion compared with similar activities in the United States.

Adolescents: at increased risk for osteoporosis?

Perhaps the most important factor in the primary prevention of osteoporosis is the attainment of an optimal peak bone during adolescence. In addition to endogenous factors, such as genetic and ethnic background, environmental factors such as dietary habits, physical activity, and sex hormone therapy, influence the accretion of bone mass during this critical period of skeletal growth. First, calcium dietary intake in adolescents is generally well less than the current recommended RDA of 1200 mg/day. Multiple studies of children and adolescents have demonstrated increases in bone mass with dietary calcium supplementation. Second, regarding physical activity, the overall impression is that a moderate amount of particularly weight-bearing exercise has a positive impact on bone. There appears, however, to be a threshold of intensity of physical activity over which a negative impact on bone occurs, particularly when the exercise is of an anaerobic nature or occurring in very thin, amenorrheic participants. Third, previous research suggests that the various forms of hormonal contraception exert differing effects on bone mass in adolescents, with levonorgestrel implants and combined oral contraceptives may be associated with a more positive effect on bone mass compared with that observed with depot medroxyprogesterone acetate. From a clinical perspective, approaches to optimizing peak bone mass in adolescents would include increasing calcium intake, whether in the form of dairy products, fortified foods, or supplements as well as encouraging participation at a moderate level, in weight-bearing exercise. Last, in adolescents with extensive risk factors and predicted long duration of use, subdermal implants or combined oral contraceptives may be the optimal hormonal methods of birth control.

Research articles published in the Journal of Adolescent Health: a two-decade comparison.

PURPOSE: To examine changes in subject contents and study designs of research articles published in the Journal of Adolescent Health since its inception. METHODS: A retrospective review of all research articles was conducted from selected years, ranging from 1980 through 1998. The study sample was composed of the following: original articles, case reports, brief scientific reports, international articles, fellowship forum, and health briefs. RESULTS: A total of 582 articles were evaluated. The total percentage of medical topics in research articles published in the Journal decreased from 61% in 1980-1981 to 38% in 1997-1998 (p <.01). This finding was in contrast to topics related to psychosocial issues, which increased from 23% to 50% (p <.01) over the same period. This change was largely accounted for by studies focusing on high-risk behavior. Retrospective designs, including case reports/series and chart reviews, decreased from 25% of all research articles in 1980-1981 to 9% in 1997-1998 (p <.01). The percentage of observational studies, i.e., those using cross-sectional and longitudinal designs, increased from 62% to 79% over the same period (p <.01). No changes were observed in the percentage of experimental designs, never exceeding >5% of total study designs. Finally, over the 20 years, professional background and academic departments of first authors of research broadened, with increasing contributions from nonphysicians and from non-pediatric disciplines such as psychology, public health, and nutrition. CONCLUSION: A shift in subject content of research articles from medical to psychosocial topics was observed over the past 2 decades. A shift in research designs from retrospective to cross-sectional and longitudinal was observed over the same period. The pool of authors has diversified.

Selections from current literature. Recent advances in conjugated pneumococcal vaccination.

This article reviews the current literature and recent updates with regard to childhood vaccination for Streptococcus pneumonia including: studies in immunology with antibody titres, dosages of conjugated vaccines, carriage rates of Streptococcus, side effects, comparison in certain disease states and comparison between vaccines.

Management of clinical side effects of DMPA.

This edition of Tips for Clinicans tackles a common patient complaint: side effects of depot medroxyprogesterone acetate (DMPA). If perception is reality, patient compliance can be greatly enhanced by addressing perception of DMPA side effects proactively. As clinicians, we can educate teens on actual as well as perceived side effects, anticipating problems and providing solutions when problems arise. Doctors Stager and Cromer provide a nice review of what to expect from DMPA and how to help.

Sexual activity and other high-risk behaviors in adolescents with chronic illness: a review.

This article is a literature review of high-risk behaviors, including sexual activity, in adolescents with chronic illness. Three different models describing biopsychosocial constructs for risky behaviors are discussed. Regarding specific behaviors, findings from the literature include a substantial prevalence of sexual activity, but low level of knowledge and low prevalence of contraceptive use, in youth with chronic illness. Regarding substance use, alcohol was the most commonly used substance regardless of medical condition. Overall, substance use, as well as delinquent behavior, was lower among youth with chronic illness when compared to that in comparison groups. Results were mixed regarding the prevalence and determinants of unhealthy eating habits in these populations. Although high-risk behaviors in teenagers with chronic illness may be a normal part of development, awareness of their prevalence, along with early identification and counseling are important in order to anticipate adverse effects on their medical conditions.

Update on adolescent contraception.

Recent advances in OCPs include less androgenic progestins and lower doses of ethinyl estradiol. All low-dose OCPs are safe in terms of venous thrombosis risk in appropriately chosen patients. DMPA is a safe and effective long-acting contraceptive agent; clinical attention should be directed to its most common side effect, irregular bleeding. DMPA does not seem to affect mood, and it is uncertain what impact it has on weight changes. More research needs to be conducted on its impact on adolescent bone metabolism. Norplant continues to be the only subdermal contraceptive implant marketed in the United States. It provides safe and effective contraception and has the best continuation rate of all types of hormonal contraception. Its most common side effect is irregular bleeding. Norplant may be especially well suited for adolescents who have recently been pregnant or who are not tolerating other types of contraception. Emergency postcoital contraception continues to be underused in the United States, with a lack of awareness among patients and clinicians. Mechanisms of action include a delay in ovulation and interference with implantation. Research and public health groups are striving to increase patient and provider awareness and use of emergency contraception.

Family planning services in adolescent pregnancy prevention: the views of key informants in four countries.

CONTEXT: Rates of adolescent pregnancy vary widely in the developed world. The prevention of adolescent pregnancy in the United States might be improved by comparing the provision of family planning services in the United States with that in some other developed countries. METHODS: Face-to-face, semi-structured interviews were conducted with 75 key informants (clinicians, politicians, public health administrators, social and behavioral scientists, and antiabortion activists) in Great Britain, the Netherlands, Sweden and the United States. Inductive, systematic qualitative analysis was performed on verbatim transcripts of these interviews. RESULTS: Across all four countries, interviewees described optimal family planning services for adolescents as those that include accessible, comprehensive and multidisciplinary care provided in confidence by nonjudgmental staff with good counseling and communication skills. Interviewees in Sweden and the Netherlands described a close liaison between family planning services and local schools, while key informants in the United States reported parental resistance to such coordination. Interviewees in the Netherlands and Sweden observed that family planning staffs in their countries have a clear sense of "ownership" of family planning services and better job-related prestige than did interviewees in Great Britain. Respondents in all countries except Sweden reported that providers are not always comfortable providing confidential care to teenagers. This was a particular concern for family planning providers in Great Britain who have patients younger than 16. Respondents in all countries except the United States thought that a "user-friendly" procedure for contraceptive provision should not require a pelvic examination. Finally, interviewees felt that governmental support in the Netherlands and Sweden seems to have led to adequate financing of family planning services, while in the United States, interviewees reported that there seems to be little governmental, medical or familial support for preventive health care, including family planning services. CONCLUSIONS: As described by key informants, the family planning services available to teenagers in the Netherlands and Sweden have many of the features identified by respondents from all four countries as those that would characterize ideal family planning services for adolescents.

PIP: The provision of family planning services in the US was compared with that of other developed countries. Data for analysis were gathered by face-to-face, semi-structured interviews among 75 key informants in Great Britain, the Netherlands, Sweden, and the US. Optimal family planning services for adolescents were observed in all four countries; the services of which include accessible, comprehensive and multidisciplinary care provided in confidence by nonjudgmental staff with good counseling and communication skills. Respondents in Sweden and Netherlands defined a close liaison between family planning services and local schools, while key informants in the US reported parental resistance to such coordination. Family planning staffs in Netherlands and Sweden were observed to have a clear sense of "ownership" of family planning services and better job-related prestige than in Great Britain. Respondents in all countries except Sweden claimed that providers are not always comfortable extending confidential care to teenagers. Respondents in all countries except the US thought that a "user-friendly" procedure for contraceptive provision should not require a pelvic examination. Finally, interviewees perceived that governmental support in the Netherlands and Sweden appears to have led to adequate funding of family planning services, while in the US, there seems to be little governmental, medical or familial support for preventive health care, including family planning services.

Recent clinical issues related to the use of depot medroxyprogesterone acetate (Depo-Provera).

This report critically reviews recent original research articles concerning patient use of depot medroxyprogesterone acetate. Specifically, recent studies have been conducted on the following clinical issues: depression, galactorrhea, weight gain, bone mineral density, epithelial and mucus changes in the lower genital tract, and the acceptability of and continuation rates with the use of depot medroxyprogesterone acetate.

The use of long-acting contraceptives in adolescents.

DMPA and implants have played an important role in the attempt to prevent teenage pregnancies. Adolescent health care providers should provide continued counseling to girls using DMPA or implants and should promptly address any concern associated with these methods. Future studies are warranted to explore ways to prevent or reduce the side effects of DMPA and implants, as well as to develop new, optimal, long-acting contraceptives. Detailed baseline information should be obtained in every future study that explores the presence of side effects during the use of long-acting contraceptives.

Comparison of continuation rates for hormonal contraception among adolescents.

BACKGROUND: Inadequate contraception is common among sexually active female adolescents, resulting in a high incidence of unwanted pregnancy. The authors were interested in comparing continuation rates for the different forms of hormonal contraception in this age group. METHODS: A retrospective chart review. The setting was an urban clinic in a large Midwestern city. Participants were 64% black, 34% white, and the average age was 15.5 years (+/- 1.6 SD), with implant users significantly older than oral contraceptive pill (OCP) users (P < .05). Interventions were self-selection to depo-medroxyprogesterone acetate (Depo-Provera; DMPA), levonorgestrel implants (Norplant), or oral contraceptive pills (OCPs). Previous pregnancy was significantly more prevalent in implant and DMPA users than in OCP users (P < .001). Over 4 years of follow-up, continuation rates were significantly higher for implant users than for the other hormonal groups (P < .001). At 1 year, continuation rates were as follows: 82% implants, 45% DMPA, and 12% OCPs. Combining these rates with those of the subsample who switched without interruption to another hormonal method, "continued protection" rates were much higher after 1 year: 96% implants, 83% DMPA, and 49% OCPs. Calculations of contraceptive "restarts," i.e., hormonal method use in those who discontinued and then restarted after a gap of time, also increased to the prevalence of contraceptive protection. CONCLUSION: Continuation rates for levonorgestrel implants were significantly higher than those for DMPA and OCPs, the latter group having the lowest continuation rates. Factoring in switches and restarts to other hormonal methods further boosted the prevalence rates of contraceptive use in the adolescent population.

Effects of hormonal contraceptives on bone mineral density.

The clinical research to date on the effects of 3 types of hormonal contraceptives, i.e. depot medroxyprogesterone acetate ('Depo-Provera'), levonorgestrel subdermal implants ('Norplant'), and oral contraceptives, on bone mineral density in premenopausal women is reviewed. The large variance in results across studies for each method is in part due to differences in research design, techniques for measuring bone mineral density, age of the study participants and type of oral contraceptive preparation. However, the balance of the evidence leans toward a positive effect of oral contraceptives on bone mineral density in women of all age. On the other hand, few observations have yet been published on the effects of the new progestin oral contraceptives on bone mineral density. The few extant data suggest a positive impact of levonorgestrel subdermal implants on bone mineral density in women of all ages. Although the findings are preliminary, it appears that depot medroxyprogesterone acetate may exert a negative effect on bone mineral density. More specifically, caution should be exercised in prescribing long term depot medroxyprogesterone acetate (e.g. > 5 years) especially in young adolescents (e.g. < 16 years old) who may not have yet reached peak bone mass.