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Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Context: Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity., Objective: To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN., Design: Double-blind, randomized, placebo-controlled trial., Setting: Clinical research center., Participants: Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women., Intervention: Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks., Main Outcome Measures: Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors., Results: Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: -2.9 ± 4.9 (testosterone) vs -3.0 ± 5.0 (placebo), P = 0.72; HAM-A: -4.5 ± 5.3 (testosterone) vs -4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo., Conclusion: Low-dose testosterone therapy for 24 weeks was associated with less weight gain-and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms-compared with placebo in women with AN., (Copyright © 2019 Endocrine Society.)

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]., Objective: To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum., Design: Cross-sectional observational study., Setting: Clinical research center., Participants: 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2)., Measures: Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA)., Results: Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone., Conclusions: Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength., (Copyright © 2017 by the Endocrine Society)

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women., (© 2015 American Society for Bone and Mineral Research.)

Heart rate variability (HRV) biofeedback, a technique which encourages slow meditative breathing, was offered to 25 in-patients with various eating disorder diagnoses-anorexia nervosa, bulimia nervosa and binge eating disorder. We found that this modality had no serious side effects, and was subjectively useful to most participants. An enhanced ability to generate highly coherent HRV patterns in patients with recent onset anorexia nervosa was observed.

The period total first abortion rate (TFAR) has been used to estimate the proportion of women who will experience an induced abortion in their reproductive lifetime. It is a hypothetical measure as age-specific rates currently existing will change with time. Instead, a cohort TFAR has been calculated for women born around 1955 using legal-abortion reports in South Australia to calculate first abortion rates for each year of age from 15 years to 44 years for 1971-2000, respectively, and summing these. Yearly fertility rates were also calculated for this cohort to further describe their reproductive experience. Yearly first abortion rates were also calculated for later cohorts born in 1960-1980. The 1955 cohort TFAR was 288.1 per 1,000 women aged 15-44 years. Cumulative first abortion rates at specific ages were higher for subsequent cohorts (e.g., 309.6 per 1,000 at age 40 years for the 1960 cohort). Thus, about 29% of South Australian women born around 1955 and exposed to legal abortion throughout their reproductive lifetime experienced an induced abortion. This proportion would be higher for later cohorts of women born in 1960-1980 (e.g., at least 31% for those born in 1960).

Objectives: To describe trends in teenage pregnancy rates in South Australia and Australia in 1970-2000, and the socio-demographic and clinical characteristics and outcomes of teenage women who gave birth in South Australia in 1995-99., Methods: A descriptive study using population-based legislated South Australian perinatal and abortion data, Australian Medicare and hospital morbidity data on abortions, and birth registration rates from the Australian Bureau of Statistics., Results: The teenage pregnancy rate in South Australia fell in the 1970s and 1980s, increased in the 1990s, but is declining at the turn of the century. Teenage abortions exceeded livebirths annually from 1994, and in 2000 the teenage abortion, birth and pregnancy rates were 22.4,18.3 and 40.8 per 1,000 respectively. The Australian rates, which are an underestimate, follow the South Australian trends and are declining but still much higher than in many western European countries. High socio-economic areas in South Australia have the lowest teenage pregnancy rates but the highest proportion of teenage pregnancies terminated. Teenagers who gave birth were more likely than older women to be Australian-born, Aboriginal, smokers during pregnancy (47% vs. 23%), to attend few antenatal visits, and to have preterm, small-for-gestational-age and low birthweight babies and neonatal deaths. Perinatal mortality has halved among teenagers under 17 years in the past decade., Conclusions and Implications: Births to South Australian teenage women are associated with social disadvantage and relatively poor perinatal outcomes, although these have improved. Current strategies are aimed at reducing the incidence of unplanned teenage pregnancy and improving support for pregnant teenagers.

Objective: To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91., Design: All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme., Setting: Southern Australia., Subjects: All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91., Main Outcome Measures: Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally., Results: Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida)., Conclusions: While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.