Table 1.

The relationship between FSH and bone health in humans.

Authors	Study design	Relationship with variables
		BMD	Bone remodelling markers	pQCT	Fracture
Premenopausal Women
Garton et al. 1996 31	68 spontaneously menstruating women aged 45-55 years. The subjects were divided based on tertiles of FSH level (<10 U/l; 10-35 U/l; >35 U/l).	Negative	Serum phosphate, PYD, DYD: positive
Sowers et al. 2003 33	2336 women aged 42- 52 years (pre and peri menopause) from the Study of Women's Health Across the Nation (SWAN). Composition of the subjects were 28.2% African-American, 49.9% Caucasian, 10.5% Japanese or 11.4% Chinese.	Negative
Sowers et al. 2003 34	2,375 pre- and early perimenopausal women from SWAN, aged 42-52 years. Multiethnicities.		NTX: positiveOsteocalcin: negative
Grewal et al. 2006 35	643 pre- and perimenopausal women, aged 43-53 years from SWAN. BMD at lumbar spine and femoral hip was measured.	Negative
Cannon et al. 2010 32	36 women aged 20-50 years with normal natural menstrual cycles.	Negative
Vural et al. 2005 59	87 healthy volunteers from the community aged 35-50 years.	Not significant	NTX: positive Osteocalcin: not significant
Hui et al. 2002 36	130 non-Hispanic white women aged 31-50 years. Followed up at least 3 times for 1-9 years.	Negative		Negative
Sowers et al. 2006 37	4-year longitudinal study of the SWAN cohort. 2311 premenopausal or early perimenopausal African-American, Caucasian, Chinese, and Japanese women.	Negative
Sowers et al. 2010 38	629 women aged 24 - 44 years at baseline were followed up for 15 years. Subjects were divided into FSH stages 1-4: 1=<15, 2=15-33, 3=34-54, 4=>54 mlU/ml.	Negative
Crandall et al. 2013 46	A 10-year follow up of 720 women in SWAN cohort. Subjects aged 42-52 (mean 46.2) years at baseline.	Negative
Women across menopausal stages
Ebeling et al. 1996 39	281 women aged 45-57 years (pre, peri and postmenopausal groups) selected from a larger randomized urban population cohort (Melbourne Women's Midlife Health Project).	Not significant after adjustment	uDPD, total PYD, NTX, BAP: positive
Perrien et al. 2006 45	188 pre- and postmenopausal women not using oral contraceptives or hormone replacement therapy (age, 21-85 yr) from Rochester Epidemiology Project. Only 2 subjects were non-Caucasians.		CTX: positiveAP, BAP, PYD, DPD: Not significant
Yasui et al. 2006 41	Cross-sectional study. 193 female outpatients of a Japanese university hospital aged 39-66 years. 40 were premenopause, 47 were perimenopause, 106 were postmenopause stage. Serum biochemical markers measured included uncarboxylated osteocalcin, intact osteocalcin, bone alkaline phosphatase, urinary N-telopeptide, LH, FSH, oestradiol, estrone.	Negative	Osteocalcin (intact and uncarboxylated): Positive
Desai et al. 2007 42	365 Indian women aged 20-70 years from a community-based clinic.	Negative
Xu et al. 2009 43	Cross-sectional study. 699 healthy Chinese women aged 20-82 years. Serum LH, FSH measured. BMD measured at posteroanterior spine, lateral spine, TH and distal forearm.	Negative
Gallagher et al. 2010 40	3247 peri- and postmenopausal women aged 42-60 years from US National Health and Nutrition Examination Survey (NHANESIII).	Negative
Wu et al. 2013 44	Cross-sectional study. 368 healthy adult Chinese women (155 premenopausal women, 63 perimenopausal, 150 postmenopausal women), aged 35-60 years.	Negative
Post-menopausal Women
Gourlay et al. 2011 47	111 community-dwelling postmenopausal women aged 50-64 years (mean 57.5 ± 3.7) from various ethnicities.	Negative but lost after adjustment
Gourlay et al. 2012 48	94 younger (aged 50 to 64 years, mean 57.5 years) community dwelling postmenopausal women not using HRT.			Negative
Wang et al. 2015 20	248 postmenopausal Chinese women aged 50 years or above (128 osteoporotic and 120 normal bone health)	Negative
Men
Karim et al. 2008 52	Case-control study. 156 community-dwelling men in London UK aged 57.7 ± 13.7 years. 63 osteoporotic men, 93 normal control.	Negative			Not significant
Hsu et al. 2015 53	1705 men aged 70 years and older from the Concord Health and Ageing in Men Project were followed up for 5 years.	Negative
Experimental by nature or human
Kawai et al. 2004 60	A retrospective study on 125 women undergoing hormone replacement therapy. Sequential measurement of hormone was performed before, at 12 and 24 months after starting hormone replacement therapy.	Negative
Devleta et al. 2004 54	7 hypergonadotropic (FSH>40 IU/l; aged 37.43 ± 3.10), 15 hypogonadotropic (FSH<40 IU/l; aged 29.8 ± 5.71) amenorrhoeic and 12 eumenorrheic women (aged 33.81 ± 5.89) were recruited.	Negative
Castelo-Branco et al. 2008 56	8 adolescent women with Kallman syndrome (hypogonadotropic); 11 with Turner syndrome (hypergonadotropic); 11 with pure gonadal dysgenesia (hypergonadotropic).	Not significant after adjustment
Drake et al. 2010 58	Post-menopausal women were randomized into two groups. One group (n=21, aged 67.4 ± 1.2) received leuprolide (7.5 mg i.m. every 28 d) and the other group (n=20, aged 66.1±1.3 years) received placebo. Both groups received aromatase inhibitor (letrozole, 2.5 mg/d) to prevent exogenous synthesis of oestradiol.		High bone turnover not inhibited.
Latoch et al. 2015 57	76 long-term survivors (43 men and 33 women) treated for paediatric cancer. 38% leukaemia, 36% lymphoma, 26% solid tumours. Age at the study was 24.1 ±3.5 years	Not significant
Tabatabai et al. 2016 55	206 women (64% white) age ≤ 55 (mean 45.9 ±5.5) years at breast cancer diagnosis receiving adjuvant cancer chemotherapy and at least 1 year after diagnosis.	Negative	CTX, PINP, osteocalcin: positiveAP, NTX: Not significant

Abbreviation:

AP=alkaline phosphatase; BAP=bone-specific alkaline phosphatase; BMD=bone mineral density; DPD=deoxypyridinoline; CTX=C-terminal telopeptide of type I collagen; FSH=follicle-stimulating hormone; NTX=N-terminal telopeptide of type I collagen; PINP=N-terminal propeptide of type I procollagen; pQCT=peripheral quantitative computed tomography; PYD=pyridinoline