To explore the clinical effect of self-made Chinese medicine prescription combined with hormone replacement for treating women with hypothalamic-pituitary amenorrhea. Methods: A total of 66 women with hypothalamic-pituitary amenorrhea were selected and randomly divided into observation group and control group (33 cases in each group) according to the random number table from January 2016 to January 2020. The women in the control group were treated with gonadotrophin supplementation only, and the women in the observation group were additionally treated with self-made Chinese medicine prescription. The levels of sex hormones, such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) before and after treatment, and the improvement of basal body temperature and the clinical effects after treatment of the women in the two groups were observed. Results: After treatment, the LH, FSH, and E2 levels of the women in the two groups had increased significantly, and which of the women in the observation group were significant higher than those of the women in the control group. The difference value of high to low basal body temperature, and variations degree of the temperature rising of the women in the two groups had increased significantly after treatment, and which of the women in the observation group were significant higher than those of the women in the control group. The total effective rate (87.9%) of the women in the observation group was significant higher than that (60.6%) of the women in the control group (all P<0.05). Conclusion: The application of traditional Chinese medicine decoction combined with exogenous sex hormone supplement therapy can effectively improve the sex hormone levels and clinical symptoms of the women with hypothalamic-pituitary amenorrhea, which has better curative effect.