Table 3.

Main outcomes from large cohort studies investigating sex steroid changes occurring in aging.

Outcomes	BLSA	MMAS	MrOS	EMAS	RBS	In CHIANTI	Tromsø	CHAMP	HIMS
Total T decline (per year)	Yes (3.2 ng/dl)	Yes (1.6%)	n.a.	Yes	Yes (1.9 pg/ml)	n.a.	Yes	Yes (2% per year)	No
T-free/bioavailable decline (per year)	Yes	Yes (2–3%)	Yes	Yes	Yes (18.5 pg/ml)	n.a.	Yes	Yes	Yes
SHBG increase	Yes	Yes	Yes	Yes	Yes	n.a.	n.a.	Yes	Yes
E2 decline (per year)	n.a.	n.a.	Yes	Yes	n.a.	n.a.	n.a.	No (↑3%)	n.a.
Sexual desire decline	n.a.	Associated to ↓TT and ↓fT	n.a.	n.a.	n.a.	n.a.	n.a.	Associated to ↓TT and ↓fT	n.a.
Erectile function decline	n.a.	Associated to ↓TT and ↓fT*	n.a.	Associated to ↓fT	n.a.	n.a.	n.a.	No association with TT and fT	n.a.
BMD impairment	n.a.	n.a.	Associated to ↓E2; conflicting data about T	Associated to ↓E2 but not to T	Associated to ↓bioavailable E2 and T	n.a.	Associated to ↑SHBG, but not with T and E2	Associated to ↑SHBG, but not with T and E2	n.a.
Increased fracture risk	n.a.	n.a.	Associated to↓ E2 and ↓ T and ↑SHBG	n.a.	n.a.	n.a.	Not associated to TT, fT, E2	Not associated to sex steroids	n.a.
Lean mass and muscle strength decline	Associated to ↓fTˆ	n.a.	Associated to ↓fT	Associated to ↓fT	n.a.	Associated to ↓TT	n.a.	Associated to ↓fT and ↓TT	n.a.
Physical performance decline	Associated to ↓fT	Associated (weakly) to ↓TT	n.a.	Associated to ↓fT	n.a.	n.a.	n.a.	n.a.	n.a.
Frailty increase	n.a.	n.a.	Associated to ↓TT	n.a.	n.a.	n.a.	n.a.	Associated to ↓TT, ↓fT, ↓E2, not to SHBG	Associated to ↓TT, ↓fT
Overweight and obesity increase	n.a.	Associated to ↓TT and ↓SHBG	n.a.	Associated to ↓TT, ↓fT, and ↓SHBG	n.a.	n.a.	Associated to ↓TT, ↓fT, ↓SHBG, and ↑E2	n.a.	Associated to ↓TT (if BMI>25)
Metabolic Syndrome risk	Associated to ↓TT and ↓SHBG	Associated to ↓TT and ↓SHBG	n.a.	n.a.	n.a.	Associated to ↓TT and ↓SHBG, and ↑E2, not to ↓fT	n.a.	Associated to ↓SHBG, not to ↓TT	Associated to ↓TT, ↓fT, ↓SHBG
Diabetes risk	n.a.	Associated to ↓TT and ↓SHBG	n.a.	n.a.	Associated to ↓TT, ↓fT	n.a.	↑TT and ↑SHBG are protective	n.a.	n.a.
CV risk increase	Arterial stifness associated to ↓TT	n.a.	Atherosclerosis associated to ↓TT	Hypertension associated to ↓TT	Hypertension associated to ↓TT	Artery disease associated to ↑SHBG, not to T and E2	Hypertension and carotid atherosclerosis associated to ↓TT	n.a.	n.a.
Low T association with poor health status and unhealthy habits	Alcohol intake associated to ↓TT	n.a.	n.a.	n.a.	n.a.	n.a.	Smoking associated to ↑TT, ↑fT, ↑SHBG	Self-reported poor status associated to ↓TT, ↓fT,	n.a.
Low T associated to reduced hemoglobin	n.a.	n.a.	n.a.	yes	n.a.	yes	n.a.	n.a.	n.a.
Low T associated to dyslipidemia	n.a.	n.a.	n.a.	yes	yes	n.a.	yes	n.a.	n.a.
Increase of all-cause mortality risk with low T	no	Weak association	yes	yes	yes	yesˆ  ˆ	yes	yesˆ ˆ ˆ	yes
CV mortality risk increase associated to low T	n.a	n.a.	n.a.	n.a.	yes	n.a.	No	Associated to↓E2	Associated to ↓fT
Cognitive function decline	Associated to ↓fT	Not associated to T	Associated to ↑SHBG	n.a.	n.a.	n.a.	n.a.	No associated to E2, T, and SHBG levels	Not associated to T
Depressive mood increase	Not associated to T	n.a.	n.a.	n.a.	Associated to↓bioavailable T	n.a	n.a.	n.a.	Associated to ↓TT

Notes. TT: Total Testosterone; fT: free Testosterone;

^*Conflicting data (association with both total and free low T, but only in more recent analyses);

^ˆmuscle strength only, not muscle and lean mass;

^ˆ  ˆ no correlation with low T alone, but with low T together with other hormones deficit;

^{ˆ ˆ ˆ}correlation with both total and free low T and with low E₂.