Supplementation with Vitamin C and/or Vitamin B6 in the Prevention of Depo-Provera Side Effects in Adolescents

Background/Objectives: Depo-Provera–induced menstrual irregularity is believed to be secondary to relative estrogen deficiency. Weight gain associated with this contraceptive method is believed to be due to Depo-Proveraʹs steroid-like appetite stimulation effect and to an altered tryptophan metabolism. We examined whether vitamin C, an important factor in uterine estrogen binding, and vitamin B6, a glucocorticoid antagonist and an important coenzyme in the tryptophan-serotonin pathway, might alleviate menstrual irregularities and weight gain associated with Depo-Provera. Methods: Fifty-five adolescent girls (age 16 ± 1 yr, gyn age 4 ± 1 yr, body mass index 25.2 ± 0.9) who decided to initiate Depo-Provera (150 mg intramuscularly every 3 months) were randomly assigned to one of four groups (group 1: vitamin B6 50 mg plus placebo pill/day; group 2: vitamin C 500 mg plus placebo pill/day; group 3: vitamin B6 50 mg plus vitamin C 500 mg/day; group 4 (control): 2 placebo pills/day) for 6 months. Participants were assessed by their care providers every 3 months. Setting: Two urban hospital-based adolescent clinics. Results: Number of days of bleeding during the first interval (first 3 months) as well as during the second interval (months 4–6) among groups 1, 2, and 3 did not differ statistically from days of bleeding in control group. There were no significant body mass index (BMI) changes among groups 1–3 (−0.15 ± 0.18, 0.34 ± 0.56, 0.01 ± 0.31) compared with control (−0.38 ± 0.38) during the first interval as well as during the second interval (0.68 ± 0.37, −0.39 ± 0.21, 0.45 ± 0.32, compared with 0.28 ± 0.43). When data from all 55 participants were collapsed, there was no significant change in BMI during the first 6 months of Depo-Provera use. About 48% at 3 months and 44% at 6 months were very or somewhat concerned about menstrual irregularity; 41% at 3 months and 18% at 6 months were very or somewhat concerned about weight changes. More than half (57%) at 3 months and 74% at 6 months reported less tampon/pad use, and 77% at 3 months and 78% at 6 months reported decreased menstrual cramps. Overall, 59% at 3 months and 70% at 6 months were very satisfied with Depo-Provera; 97% at 3 months and 96% at 6 months said that they would recommend Depo-Provera to a friend or a relative. Conclusions: This study does not support a role for vitamin C in the prevention of Depo-Provera–induced menstrual irregularities or for vitamin B6 in the prevention of weight changes associated with Depo-Provera. The unchanged BMI during the first 6 months of Depo-Provera use in the present study suggests that raising awareness and close follow-up may prevent weight gain among adolescent girls using this contraceptive method.