Bone health in anorexia

The acquisition of bone mass during adolescence is vital to the development of normal bone density later in life. Adolescent girls with anorexia nervosa have low
bone mineral density (BMD) secondary to decreased lean body mass, hypogonadism, decreased insulin like growth factor-1 (IGF-1) and other hormonal factors. The first of these two articles reviews the current knowledge concerning this issue. It has previously been demonstrated that women who had anorexia nervosa as adolescents have a lower BMD later in life, when compared to women in whom anorexia did not occur until adulthood, even if the total duration of amenorrhoea was the same. Gynaecologists may encounter these girls as part of assessment and treatment of amenorrhea. It is reported that if weight is gained and menses return then there is an increase of BMD of 1.4 per cent at the spine after one year, compared with an decrease of 0.3 per cent girls who remain amenorrhoeic and a three per cent increase in normal weight controls.

Treatment of anorexia nervosa can be extremely difficult and some women will remain amenorrhoeic for a number of years despite treatment. Some researchers have investigated the effect of oestrogen replacement on BMD in adolescents with anorexia nervosa. In the second article Misra et al. report the results of physiological levels of oestrogen replacement on BMD in adolescent girls with anorexia nervosa. In a placebo controlled trial of over 100 girls aged between 12 and 18 with anorexia nervosa, the authors compared placebo to low-dose ‘physiological’ oral ethinyl-oestradiol in girls who had not yet reached bone maturity and higher dose transdermal 17β-ooestradiol (with cyclic progesterone) in girls who had reached bone maturity. In both age groups the girls receiving oestrogen showed an increase in BMD after 18 months of treatment compared to the placebo groups. Interestingly, previous research cited by the authors found that oral oestrogen replacement given as the combined oestrogen-progestin oral contraceptive pill did not increase BMD in girls with anorexia nervosa, possibly due to suppression of IGF-1 by the pill. It should, however, be noted that oestrogen replacement alone will not return BMD to normal levels in these girls, due to the multifactorial mechanism of BMD reduction in anorexia nervosa.

Misra, M, Klibanski, A. 2011. Bone health in anorexia nervosa. Current Opinion in Endocrinology, Diabetes & Obesity, 18: 376-382.Misra, M, Katzmann, D et al. 2011. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. Journal of Bone and Mineral Research, 26: 2430-2438.

Ultrasound and β-hCG in early pregnancy

A relatively common situation in early pregnancy arises when a woman presents with a quantitative β-hCG result and an ultrasound, with the question of whether her pregnancy is likely to be ongoing. It is a commonly held belief that if the β-hCG is greater than the discriminatory level of 1500-2000mIU/mL, then evidence of an intrauterine pregnancy should be visible on transvaginal ultrasound. This recent American paper reports the pregnancy outcomes on over 200 women who had both a β-hCG and transvaginal ultrasound performed on the same day without finding an intrauterine fluid collection suggestive of a gestational sac and in whom a live intrauterine pregnancy was later documented. The results showed that over ten per cent of these women had an initial β-hCG level of >1500mIU/mL. The highest initial β-hCG level in which a live term baby was later delivered after there being no ultrasound evidence of an intrauterine pregnancy was 4336mIU/mL. The authors reasonably conclude that: ‘The hCG discriminatory level should not be used to determine the management of a haemodynamically stable patient with suspected ectopic pregnancy, if sonography demonstrates no findings of intrauterine or ectopic pregnancy.’

Doubilet, PM, Benson, CB. 2011. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. Journal of Ultrasound in Medicine. 30: 1637-42.

Ulipristal for fibroids

Ulipristal is an oral selective progesterone receptor modulator that is not currently available in Australia or New Zealand. It is available in some European countries and in the USA. Initially used primarily for emergency contraception, two recent European studies report on the efficacy of ulipristal in the treatment of fibroids.

In the first study the authors randomly assigned 194 women with symptomatic fibroids and anaemia to receive 13 weeks of either daily oral ulipristal or placebo. The results after 13 weeks showed control of uterine bleeding in over 90 per cent of women receiving ulipristal, compared to 19 per cent in women receiving placebo, with amenorrhea in over 70 per cent of women receiving ulipristal compared to six per cent in women receiving placebo. The ulipristal group also showed a significantly greater reduction in uterine volume compared with the placebo group.

A second study by the same group was a randomised double-blind non-inferiority trial comparing 13 weeks of oral ulipristal to 13 weeks of leuprolide (delivered as monthly intramuscular injections of 3.75 mg each). The authors concluded that oral ulipristal was non-inferior to intramuscular leuprolide in controlling uterine bleeding and significantly less likely to cause hot flashes. While this treatment option is not currently available in Australia or New Zealand, these studies suggest it may become an additional medical treatment option for fibroids at a later date.

Donnez, J, Tatarchuk, TF et al. 2012. Ulipristal Acetate versus Placebo for Fibroid Treatment before Surgery. New England Journal of Medicine, 366:409-20.
Donnez, J, Tomaszewski, J et al. 2012. Ulipristal Acetate versus Leuprolide Acetate for Uterine Fibroids. New England Journal of
Medicine, 366:421-432.