Poikkileikkaustutkimuksessa «Seeman E, Szmukler GI, Formica C ym. Osteoporosis in anorexia nervosa: the influence of peak bone density, bone loss, oral contraceptive use, and exercise. J Bone Miner Res 1992;7:1467-74 »1 lanneselän luuntiheys oli merkitsevästi korkeampi 16:lla laihuushäiriöpotilaalla, jotka käyttivät ehkäisypillereitä kuin 49:lla kontrollipotilaalla, jotka eivät käyttäneet estrogeenia. E-pilleri ei kuitenkaan parantanut laihuushäiriöpotilaiden reisiluunkaulan luuntiheyttä. Reisikaulan luuntiheys oli suurempi 19:llä laihuushäiriöpotilaalla, jotka harrastivat liikuntaa verrattuna 30:een laihuushäiriöpotilaaseen, jotka eivät harrastaneet liikuntaa.

• Tutkimuksen laatu: kelvollinen
• Sovellettavuus suomalaiseen väestöön: hyvä

Satunnaistetussa etenevässä kontrolloidussa tutkimuksessa «Klibanski A, Biller BM, Schoenfeld DA ym. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 1995;80:898-904 »2 verrattiin laihuushäiriöpotilailla konjugoitua estrogeenia ja medroksiprogesteroniasetaattia (n=22) lumehoitoon (n=26). Puolentoista vuoden hoidon jälkeen spinaaliluuntiheys ei lisääntynyt hormonilääkettä saaneilla potilailla lumehoitoryhmään verrattuna. Ainoastaan potilailla, joilla paino oli alle 70 % ihannepainosta, luuntiheys lisääntyi 4 % lähtötasosta, kun kontrollipotilailla se väheni 20.1 % (ARR 18 %, NNT 5.6). Näin ollen hormonikorvaushoidosta voisi olla hyötyä luukadon estossa vain laihuushäiriöpotilailla, joilla paino on hyvin alhainen.

• Tutkimuksen laatu: tasokas
• Sovellettavuus suomalaiseen väestöön: hyvä

This prospective observational study «Golden NH, Lanzkowsky L, Schebendach J ym. The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J Pediatr Adolesc Gynecol 2002;15:135-43 »3 investigated the effect of estrogen-progestin administration on bone mass in 50 adolescents with anorexia nervosa (mean age 16.8 +/- 2.3 yrs). Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually. Twenty-two subjects received estrogen-progestin and standard treatment and 28 standard treatment (Rx) alone. Estrogen-progestin was administered daily as an oral contraceptive containing 20–35 mcg ethinyl estradiol. All subjects received calcium supplementation and the same medical, psychological, and nutritional intervention (standard Rx). Mean length of follow-up was 23.1 +/- 11.4 months. At presentation, 92% of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx. In those followed for 2–3 yrs, osteopenia was persistent and in some cases progressive.

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In this cross-sectional study «Karlsson MK, Weigall SJ, Duan Y ym. Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa. J Clin Endocrin»4 the following questions were asked: 1) Is anorexia nervosa associated with reduced bone size and reduced volumetric bone mineral density (vBMD)? 2) Is estrogen replacement therapy (ERT) or recovery from anorexia nervosa associated with normal bone size and vBMD? Using dual-energy x-ray absorptiometry, bone size and vBMD of the third lumbar vertebra and femoral neck were measured in 161 female patients: 77 with untreated anorexia nervosa, 58 with anorexia nervosa receiving ERT, 26 recovered from anorexia nervosa, and 205 healthy age-matched controls. Results: Deficits in bone width were less in the ERT-treated women than in untreated women at the vertebral body, but not at the femoral neck. There were no significant deficits in vertebral body and femoral neck width in recovered women. In untreated women, vertebral and femoral neck vBMD were -1.6 +/- 0.1 and -1.1 +/- 0.1 SD, respectively (both P < 0.001), less severely reduced in ERT-treated women (-1.2 +/- 0.2 and -0.6 +/- 0.2 SD, respectively; both P < 0.001), and least reduced in recovered women (-0.6 +/- 0.1 and -0.5 +/- 0.2 SD; P < 0.01 and P < 0.05, respectively). After adjusting for differences in fat and lean mass, vertebral body and femoral neck width were no longer reduced in untreated, ERT-treated, and recovered women. Adjustment for body composition had little effect on group difference in vBMD. Conclusion: Bone fragility in anorexia nervosa is due to reduced bone size and reduced vBMD. Although causality cannot be inferred in cross-sectional studies, the data are consistent with the view that malnutrition may contribute to reduced bone size, whereas estrogen deficiency may reduce vBMD. The use of ERT early in disease is a reasonable component of management if the chance of recovery appears remote.

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In this randomized placebo-controlled study «Strokosch GR, Friedman AJ, Wu SC ym. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-cont»5 females 11–17 years of age with AN (anorexia nervosa) or ENOS (eating disorder not otherwise specified) were randomized (double-blind) to a triphasic OC containing norgestimate (NGM) 180-250 microg and ethinyl estradiol (EE) 35 microg (n=53) or placebo (n=59) for 13 28-day cycles. Dual energy x-ray absorptiometry scans (DXA) of the lumbosacral spine (LS) and hip were obtained at baseline and after 6 and 13 cycles. Results: At the end of Cycle 6, there was a significant increase in the mean LS BMD in the NGM/EE group compared with placebo (.020 g/cm² vs. .008 g/cm²; p = .021); however, at the end of Cycle 13 the mean increase in LS BMD in the NGM/EE group compared with placebo was no longer significant. There was no significant difference in change in hip BMD between groups. The incidence of adverse events was similar between groups. Conclusions: In a group of adolescent females with AN or EDNOS, treatment with a triphasic OC for 13 cycles did not have a statistically significant effect on LS or hip BMD.

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The objective of this cross-sectional study «Miller KK, Lawson EA, Mathur V ym. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metab 2007;92:1334-9 »6 was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in these women. Intervention and patients: A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Outcomes: Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results: Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusion: Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women.

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The hypothesis of this study «Grinspoon S, Thomas L, Miller K ym. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab 2002;87:2883-91 »7 was to investigate whether recombinant human IGF-I (rhIGF-I) increases bone density in women with anorexia nervosa. Aim of the study: To assess the effects of combined rhIGF-I and oral contraceptive administration (OCP) in this population. Patients and methods: Sixty osteopenic women with anorexia nervosa [age (25.2 +/- 0.7 yr, range 18-38 yr), body mass index (17.8 +/- 0.3 kg/m(2) ), spinal bone mineral density T score (-2.1 +/- 0.1 SD) were randomized to one of four treatment groups [rhIGF-I (30 microg/kg sc twice daily) and a daily oral contraceptive (Ovcon 35, 35 microg ethinyl estradiol and 0.4 mg norethindrone], rhIGF-I alone (30 microg/kg sc twice daily), oral contraceptive alone, or neither treatment for 9 months. All subjects received calcium 1500 mg/d and a standard multivitamin containing 400 IU of vitamin D. Administration of rhIGF-I was placebo controlled and blinded to subjects. Results: Anteroposterior spinal bone density increased significantly in response to rhIGF-I.. In contrast, OCP did not result in increased bone density. However, bone density increased to the greatest extent in the combined treatment group (rhIGF-I and OCP), compared with control patients receiving no active therapy. Conclusions: Osteopenic women with anorexia nervosa treated with rhIGF-I showed more beneficial changes in bone density, compared with patients not treated with rhIGF-I. Antiresorptive therapy with OCP is not sufficient to improve bone density in undernourished patients, but such therapy may augment the effects of rhIGF-I in a combined treatment strategy.

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• Sovellettavuus suomalaiseen väestöön: hyvä

Hormonikorvaushoidon vaikuttavuudesta laihuushäiriöpotilaiden luukadon hoidossa ei ole varmuutta. Satunnaistetussa tutkimuksessa «Klibanski A, Biller BM, Schoenfeld DA ym. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 1995;80:898-904 »2 hormonikorvaushoito paransi luuntiheyttä ainoastaan niillä laihuushäiriöpotilailla, joiden lähtöpaino oli selvästi alle ihannepainoa, ja toisessa prospektiivisessa tutkimuksessa vuoden kestävä estrogeeni-progestiinihoito ei parantanut luuntiheyttä verrattuna standardihoitoon «Golden NH, Lanzkowsky L, Schebendach J ym. The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J Pediatr Adolesc Gynecol 2002;15:135-43 »3. Estrogeenikorvaushoidosta saattaa kuitenkin olla hyötyä potilaille, joilla on odotettavissa pitkään kestävää toipumista «Karlsson MK, Weigall SJ, Duan Y ym. Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa. J Clin Endocrin»4. Ehkäisypillerihoito ei parantanut luuntiheyttä lumelääkkeeseen verrattuna «Strokosch GR, Friedman AJ, Wu SC ym. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-cont»5, ja toisessa tutkimuksessa e-pillerihoito näytti jopa heikentävän luustontiheyttä laihuushäiriöpotilailla «Miller KK, Lawson EA, Mathur V ym. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metab 2007;92:1334-9 »6. Vaikka rhIGF-I ja oraalisen estrogeenihoidon yhdistelmähoito saattaisi parantaa luun tiheyttä aikuisilla laihuushäiriöpotilailla, lääke on kallis, sillä on merkittäviä haittavaikutuksia, joten sitä ei tällä hetkellä tule käyttää anoreksia potilaiden hoidossa «Grinspoon S, Thomas L, Miller K ym. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab 2002;87:2883-91 »7.

Kaikissa RCT:ssa potilaiden määrät ovat suhteellisen pieniä ja seuranta-ajat lyhyet. Estrogeenikorvaushoidon vaikutuksesta murtumien esiintyvyyteen tai elämän laatuun ei ole olemassa tutkimuksia.