Bone mineral density in young women with long-standing amenorrhea: Limited effect of hormone replacement therapy with ethinylestradiol and desogestrel

Abstract

To assess bone mineral density (BMD) at different skeletal sites in women with hypothalamic or ovarian amenorrhea and the effect of estrogen-gestagen substitution on BMD we compared BMD of 21 amenorrheic patients with hypothalamic or ovarian amenorrhea with that of a control population of 123 healthy women. All amenorrheic patients were recruited from the outpatient clinic of the Division of Gynecological Endocrinology at the University of Berne, a public University Hospital. One hundred and twenty-three healthy, regularly menstruating women recruited in the Berne area served as a control group. BMD was measured using dual-energy X-ray absorptiometry (DXA). At each site where it was measured, mean BMD was lower in the amenorrheic group than in the control group. Compared with the control group, average BMD in the amenorrheic group was 85% at lumbar spine (p < 0.0001), 92% at femoral neck (p < 0.02), 90% at Ward's triangle (p < 0.03), 92% at tibial diaphysis (p < 0.0001) and 92% at tibial epiphysis (p < 0.03). Fifteen amenorrheic women received estrogen-gestagen replacement therapy (0.03 mg ethinylestradiol and 0.15 mg desogestrel daily for 21 days per month), bone densitometry being repeated within 12-24 months. An annual increase in BMD of 0.2% to 2.9% was noted at all measured sites, the level of significance being reached at the lumbar spine (p < 0.0012) and Ward's triangle (p < 0.033). In conclusion BMD is lower in amenorrheic young women than in a population of normally menstruating, age-matched women in both mainly trabecular (lumbar spine, Ward's triangle, tibial epiphysis) and mainly cortical bone (femoral neck, tibial diaphysis).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oral contraceptives and hormone replacement therapy on bone mineral density in premenopausal and perimenopausal women: a systematic review

“…Of the 10 studies of OC and other hormone replacement in this population, seven (two RCTs, 62 63 five cohort [64][65][66][67][68] ) showed a positive effect, two (one RCT, 69 one cohort 70 ) showed no effect, and one case report 71 showed a negative effect on BMD. In all studies that compared baseline BMDs with that of healthy controls or age matched reference values, baseline BMDs were significantly lower in the oligo/amenorrhoeic subjects.…”

“…In all studies that compared baseline BMDs with that of healthy controls or age matched reference values, baseline BMDs were significantly lower in the oligo/amenorrhoeic subjects. [65][66][67][68][69][70][71] Hergenroeder et al 62 showed an increase in total body and lumbar spine BMD with OCs, compared with medroxyprogesterone or placebo. Although well designed, this was a small study with only five subjects per treatment group, followed over a 12 month time span.…”

“…Menstrual irregularities were classified as ''hypothalamic'' oligo/amenorrhoea-that is, functional menstrual irregularity-or that occurring in the absence of an organic cause (except for two cohort studies which included subjects with primary ovarian failure, 66 and from a variety of unspecified causes 65 ). Although these conditions often occur in athletic females, as previously discussed, it is the energy Oral contraceptives/hormone replacement and bone mineral density deficit, rather than the activity itself, that leads to the menstrual dysfunction.…”

The Female Athlete Triad

“…In a cohort study of anorexia nervosa patients, adjustment for weight gain cancelled out apparent effects of HRT (64). Evidence of the effectiveness of OCP for increasing BMD in athletes and other women with functional hypothalamic amenorrhea without eating disorders is also mixed (119), with some randomized clinical trials and cohort studies finding partial recovery (32,40,69,71,76,163,205) and others not (61,66), but concurrent changes in body weight were often not reported. One study reported that the increase in BMD was accompanied by an increase in weight (163) and another reported that the effect of weight gain exceeded the effect of OCP (69).…”

Antipsychotics and hyperprolactinaemia: pathophysiology, clinical significance, clarification and therapy

“…Eine primäre oder sekundäre Amenorrhö führt mit oder ohne Hyperprolaktinämie zu einer verminderten Knochendichte mit erhöhtem Frakturrisiko [26,81]. Un ter Antipsychotika wurde verschiedent lich eine reduzierte Knochendichte gefun den [1,3,30,33,35,40,51,52,60], wobei die Studien bezüglich des Kausalzusammen hanges nicht einheitlich sind.…”