OBJECTIVE: To explore the clinical application value of routine regimen of estrogen combined with and progesterone in the treatment of female postmenopausal osteoporosis. METHODS: 126 patients with postmenopausal osteoporosis were randomly divided into combination group (group A) and routine group (group B), with 63 cases in each group. Group B was treated with routine treatment, such as calcium and vitamin D, while group A was additionally treated with estrogen and progesterone on the basis of routine treatment. The bone mineral density (BMD), numeric rating scores (NRS) and Pittsburgh sleep quality index (PSQI) scores were compared between 2 groups before and after treatment. The levels of serum bone gla protein (BGP), blood bone alkaline phosphatase (BAP), serum calcitonin (h-CT) and parathyroid hormone (PTH) were also compared between 2 groups before and after treatment, and the occurrence of ADR was recorded. RESULTS: After treatment, BMD of 2 groups were significantly higher than before, and NRS and PSQI were significantly lower than before, with statistical significance (P<0.001); the improvement of each index in group A was greater than in group B, with statistical significance (P<0.001). After treatment, the levels of BGP and h-CT in 2 groups were significantly improved, compared with those before treatment while levels of BAP and PTH were significantly lower than those before treatment, with statistical significance (P<0.001); the improvement of each index in group A was greater than in group B, with statistical significance (P<0.01). No serious ADR was found in 2 groups after medication. The incidence of mild ADR in group A was 19.0%; compared with 17.5% in group B, there was no statistical significance (P>0.05). CONCLUSIONS: For patients with postmenopausal osteoporosis, conventional treatment combined with estrogen and progesterone shows definite therapeutic efficacy, and can effectively improve BMD value, relieve the pain symptoms and has positive effect on promoting prognosis and improving the prognosis.