Clomiphene citrate as a new modality in management of vaginal bleeding with depomedroxyprogesterone acetate (DMPA): A randomized controlled trial

• Published in: Steroids Vol. 206; p. 109425
• Main Authors: Shaheen, Kareem, Kamel, Hany H., Mostafa Mohammed, Enas, Hashim Mohammed, Ahmed, Ahmed Sileem, Sileem, Fouad, Mahmoud, Shehata Sayd, Zainab, ElHodiby, Mohamed E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Adult; Clomiphene - adverse effects; Clomiphene - therapeutic use; Clomiphene citrate; Contraception; Depo-medroxyprogesterone acetate; DMPA; Female; Humans; Medroxyprogesterone Acetate - administration & dosage; Medroxyprogesterone Acetate - adverse effects; Uterine Hemorrhage - chemically induced; Uterine Hemorrhage - drug therapy; Young Adult; CC; Depo-medroxyprogesterone acetate; DMPA; Contraception; Clomiphene citrate
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2024.109425

•DMPA is an effective contraceptive method, with a low annual failure rate of 0.3 %.•Breakthrough bleeding is a common side effect among DMPA users.•Our aim was to assess the efficacy of CC to control bleeding among DMPA users.•CC resulted in early cessation of vaginal bleeding in 83 % of the patients.•The recurrence of vaginal bleeding was significantly reduced in the CC group. Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users. We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use. Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups. Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.