Treatments to Prevent Bone Loss in Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis

Abstract

Objective:We conducted a systematic review and meta-analysis of studies that evaluated the effect of hormonal therapy [estrogen therapy including oral contraceptive pills (OCP)] and bisphosphonates in preventing bone loss in patients with functional hypothalamic amenorrhea (FHA).Methods:We searched several electronic databases for controlled and noncontrolled studies that enrolled females of any age presenting with FHA (including athletic, weight loss, and stress-associated amenorrhea/oligomenorrhea) through 9 January 2017. The outcomes of interest were fractures and bone mineral density (BMD). Random effects meta-analysis was used to pool outcomes across studies expressed as weighted mean difference and 95% confidence interval (CI).Results:Nine studies reporting on 280 patients that received different hormonal therapies were included. We did not identify studies that evaluated bisphosphonates. Meta-analysis demonstrated a statistically significant increase in BMD of the lumbar spine in patients receiving hormonal therapy after a median follow-up of 12 months (weighted mean difference, 0.032 g/cm2; 95% CI, 0.017 to 0.047; percentage change in BMD, 3.30%; 95% CI, 1.74 to 4.86). There was no substantial effect of receiving hormonal therapy on BMD of the femoral neck, trochanteric region, Ward triangle, or total body BMD. The quality of evidence was low because of the high risk of bias, imprecision (small sample size), and indirectness (as BMD is a surrogate outcome). None of the studies reported the incidence of fractures.Conclusion:The current evidence does not support using hormonal therapy for the sole purpose of improving bone health in patients with FHA. There are no data about bisphosphonates in this population.

Risk Factors, Diagnosis and Management of Bone Stress Injuries in Adolescent Athletes: A Narrative Review

“…The aim of this intervention is to improve BMD through oestrogen replacement however, more research is required. Oral contraceptives do not restore BMD in athletes and in some cases, are detrimental to BMD [ 115 , 181 , 182 , 183 ]. Irrespective of oestrogen supplementation in the adolescent athlete, potential underlying causes of amenorrhea (energy availability, pituitary issues, ovarian issues, thyroid) should be addressed [ 180 ].…”

“…Medications typically administered to older persons with osteopenia or osteoporosis (bisphosphonates) are in most cases not appropriate for adolescent athletes, particularly females, due to their potential teratogenic effects and long-half life in bone [ 184 ]. Although case studies have evaluated intravenous bisphosphonates for young adult athletes prone to stress fracture, RCTs investigating the effectiveness and safety of this method of treatment in adolescent athletes or Female Athlete Triad are lacking [ 106 , 181 ]. Bisphosphonates (risedronate) did not prevent stress fracture in Israeli army recruits (mean age 19.1 ± 1.2) [ 185 ].…”

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

“…The most commonly prescribed treatment for bone loss in premenopausal women with FHA is oral contraceptives (OCPs) or conjugated oestrogens (CE) to improve hypo-oestrogenic environment and, theoretically, protect bone. Systematic reviews have not found OCPs to significantly improve BMD in women with athletic FHA [14][15][16] or anorexia nervosa (AN). 14 17 18 However, some recent randomised controlled trials (RCTs) have reported that transdermal estradiol (TE) is effective in increasing BMD in anorexic and amenorrhoeic premenopausal women.…”

Effect of Alkaline Drinking Water on Bone Density of Postmenopausal Women with Osteoporosis

“…One of the factors that disturb this balance in women is menopause because of physiological and biochemical changes, increased turnover, increased bone resorption [ 7 8 9 ]. The main purpose of treatment is to prevent bone loss and increase bone formation [ 8 10 ].…”