Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials - Summary - MDSpire

Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials

  • By

  • Agathoklis Efthymiadis

  • Konstantinos Tsikopoulos

  • Edouard G Mills

  • Andrew Milne

  • Waljit S Dhillo

  • Ali Abbara

  • Alexander N Comninos

  • January 8, 2026

  • 0 min

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Objective:

To compare the efficacy of pharmacological interventions for improving bone mineral density (BMD) in women with functional hypothalamic amenorrhea (FHA), addressing treatment gaps.

Key Findings:
  • Transdermal hormone replacement therapy (HRT) improved lumbar spine BMD (SMD: 0.34) and femoral neck BMD (SMD: 0.57) compared to control, based on two trials.
  • Oral HRT and combined oral contraceptive pill (COCP) showed no significant benefit for any BMD site across multiple trials.
  • Teriparatide was superior to transdermal HRT and COCP for lumbar spine BMD (SMDs: 1.48 and 1.75, respectively), but not for femoral neck or total hip BMD.
Interpretation:

Transdermal HRT and teriparatide are effective in improving lumbar spine BMD in women with FHA, with transdermal HRT also benefiting femoral neck BMD, suggesting a need for clinical adoption.

Limitations:
  • Evidence for transdermal HRT is based on only two randomized-controlled trials.
  • Low certainty in recommendations for COCP use due to lack of prospective studies.
  • Potential biases in the included studies may affect the reliability of findings.
Conclusion:

There is a critical need for more robust evidence to guide pharmacological treatment recommendations for bone health in women with FHA.

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