Table 1.

Study characteristics.

Study	Pharmacological agent	Dose	Type of study	Follow-up	Outcome measures	Sig. change in outcome measure(s)	Quality assessment	Grade of evidence
Bloch 2012	DHEA	100 mg/day	Double-blind placebo controlled RCT	6 months	Total body Spinal Hip Femoral Neck	NS	1	B
DiVasta 2012	DHEA OC: EE/levonorgestrel	50 mg 20 μg/0.1 mg	Double-blind placebo controlled RCT	6, 12 and 18 months	Lumbar spine Hip Whole body	Stabilising effect	2	B
Fazeli 2014	Teriparatide (TPt)	20 μg/day SC	Double Blind RCT	3 and 6 months	Posteroanterior spine Lateral Spine Hip Femoral neck	Sig. (spinal only)	1	A
Golden 2002	OC: EE/progestin	20–35 μg EE/day	Prospective observational study	11.4–23.1 months	Lumbar spine Femoral neck	NS	2	C
Golden 2005	Alendronate	10 mg/day	Double-blind placebo controlled RCT	3, 6, 9 months and 1 yr	Lumbar spine Femoral neck	NS	2	B
Gordon 1999	DHEA	50, 100, or 200 mg/day	Controlled trial	3 month	Lumbar spine Total body Femoral neck	NS	2	C
Grinspoon 1996	rhIGF1	100 or 30 μg/kg/day	Controlled trial	6 days	OC PICP PYRX DPYRX NTX	Sig increase in all markers (100 μg/day) Sig, increase in PICP only (30 μg/day)	2	B
Grinspoon 2002	rhIGF-1 EE with rhIGF-EE+ placebo	30 μg/kg SC twice/day 35 μg/day + 30 μg/kg SC twice/day 35 μg/day	Double-blind placebo controlled RCT	12 weeks	Lateral spine BMD Hip BMD Femoral neck BMD Total body BMD	NS	2	B
Iketani 2003	MED	45 μg/day	Controlled trial	0.9 yr	Lumbar spine	Stabilising effect	2	C
Karlsson 2000	Estrogen replacement therapy	Various	Retrospective cohort study	4.3 yr (1–16 yr range)	Lumbar Spine Femoral neck	NS	2	C
Misra 2009	RhIGF1	30–40 mcg/k twice daily	Double-blind placebo controlled RCT	7–9 days	IGF1 P1NP CTX	Sig. increase in IGF1 and P1NP	1	A
Misra 2011	Transdermal: 17b-estradiol with cyclic progesterone Oral: EE + progesterone	100 mg/day 3.75 mg/7.5 mg/11.25 mg/day	Double-blind placebo controlled RCT	18 months	Lumbar spine Hip	Sig.	1	A
Miller 2011	Risedronate (R) Transdermal testosterone (T) Combination	35 mg/week 150 μg/day R:35 mg/week T: 150 μg/day	Double-blind placebo controlled RCT	12 months	Spinal BMD Hip, and radius BMD Body composition	Sig. (R)	1	A
Miller 2004	Risedronate	5 mg/day	Controlled trial	6 months, 9 months	Spinal BMD	Sig.	1	A
Miller 2005	Transdermal testosterone	150 μg/300 μg/day	Double-blind placebo controlled RCT	3 weeks	Spinal BMD	NS	1	B
Munoz 2002	OC: EE	30 μg/day	Controlled trial	12 months	Spinal BMD	NS	2	C
Seeman 1992	OC: Various	Various	Prospective observational study	61 months ± 9% duration of illness	Spinal BMD Femoral Neck BMD	Sig. (spinal)	2	C2
Shibli-Rahhal 2012	Teriparatide (TPt)	20 mcg/day	Case study	2 yr	Lumbar spine Femoral neck	Sig.	2	D
Strokosch 2006	OC: Norgestimate (NGM) OC: EE	180–250 μg/day 35 μg/day	Double-blind placebo controlled RCT	13 consecutive 28 day cycles	Lumbar spine BMD	NS	1	B

Study characteristics of included studies in the systematic review. ‘Spinal’ refers to measurement of BMD at the lumbar spine. BMD = Bone Mineral Density, aBMD = areal Bone Mineral Density. (n) = number, SC = subcutaneous injection, NS = non-significant, Sig. = statistically significant (p < 0.05), AN = Anorexia Nervosa, HC = Healthy Controls, BMI = Body Mass Index, Tpt = teriparatide, EE = ethinyl estradiol, ERT = estrogen replacement therapy. NGM = Norgestimate, OC = oral contraceptives, MED = Menatetrenone.