Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis

BackgroundFemale athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake.ObjectiveTo systematically review the literature of randomised controlled trials (RCTs) assessing the effect of oestrogen oral contraceptives (OCP), conjugated oestrogens (CE) and transdermal estradiol (TE) on BMD in premenopausal women with functional hypothalamic amenorrhoea (FHA) due to weight loss, vigorous exercise and/or stress.MethodsA comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020.Data extraction and synthesisTwo authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis.Main outcomesDifference in BMD (g/cm2) at the lumbar spine.ResultsNine RCTs comprising 770 participants met the inclusion criteria; five studies applied OCP, two CE and two TE. Four RCTs (two OCP, two TE) found an increased BMD in premenopausal women with FHA, and five (three OCP, two CE) found a decreased BMD compared with controls. A meta-analysis showed no difference in BMD between the treatment and control groups, (standardised mean difference (SMD) 0.30, 95% CI −0.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95% CI −0.16 to 0.51). No serious adverse events were reported.ConclusionThe literature suggests that TE might increase lumbar BMD in premenopausal women with FHA, but pooled results revealed no effect of the intervention. The findings do not support oestrogen therapy to improve BMD in these patient groups.

Breast cancer anti-hormonal therapy and rheumatic diseases: linking the clinical to molecular world

Anti-hormonal therapies are used in the treatment of hormone dependent breast cancer. Their use may be complicated with the onset of arthralgia and autoimmune diseases. Recently a clinical relationship between oestrogen, anti-oestrogen therapy and rheumatic diseases has been reported in the literature, but, until now, experimental supporting data about the interacting biochemical pathways involved are still very limited. The understanding of this molecular link may provide important information to elucidate the relationship between autoimmunity and cancer mechanism and treatment. This review is intended to highlight the relationship between known common molecular mechanisms which explain this association and that probably need to be investigated in future studies.