The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different hormone therapies, including hormonal contraceptives, in women with premature ovarian insufficiency (POI). Thirty reports of 28 studies were included, with a total of 4004 participants with POI from diverse aetiologies, of whom 3785 received hormone therapies and 219 received calcium supplementation, vitamin D, placebo or no treatment. Hormone therapy was superior to non-treatment, placebo, calcitriol or calcium in preserving bone mineral density (BMD) in women with POI. Hormone therapy was associated with up to 80% reduction in the prevalence of hot flushes and with stability or improvement in the quality of life scores. Hormone therapy induced significant increases in uterine volume and endometrial thickness in women with POI. The studies yielded convergent results and were of good quality, although some lacked blinding or had incomplete outcome data. Moderate to high quality evidence was found that hormone therapy with oestrogen and progesterone or progestin (including contraceptives) is beneficial to women with POI, not only to mitigate hypoestrogenic symptoms but also to preserve BMD and avoid uterine atrophy. More studies are needed to confirm the long-term safety of this therapy and to assess its possible impact on the risk of hard outcomes such as bone fractures and cardiovascular events.