Tryptophan metabolism in women using steroid hormones for ovulation control.

PIP: This is an extension of work recently reported by Rose regarding young women using a combination of progesterone and estrogen for ovulation control. The 10 subjects studied had an abnormal xanthurenic acid excretion after a loading dose of tryptophan. After treatment with 2.5 mg norethynodrel and .1 mg mestranol (Enovid-E) from Days 5 to 24 of the the cycle, 24-hour urine specimens were collected before and after administration of 2 gm of L-tryptophan. They were then given 25 mg of pyridoxine hydrochloride 4 times a day during the 48 hours required to repeat the tryptophan loading test. Controls were 18 healthy women not taking drugs. Metabolites of trytophan determined were indican, anthranilic acid glucuronide, 0-aminohippuric acid, kynurenic acid, acetylkynurenine, kynurenine, 3-hydroxykynurenine, xanthurenic acid, and N-methyl-2-pyridone-5-carboxamide. Urine specimines were analyzed for these and for 4-pyridoxic acid taking usual precautions to avoid dietary factors or drugs which might vitiate the results. At first the ingestion of the steroid had no significant effect on the basal excretion of urinary tryptophan metabolites. However, after the loading dose of tryptophan, the subjects taking Enovid E- excreted a mean level of 697 micro-moles of xanthurenic acid compared with a mean level of 29.8 micro-moles in controls. Some of the other metabolites were also excreted in increased quantities: 3-hydroxykynurenine, kynurenine, kynurenic acid, and acetylkynurenine. The others were excreted in normal quantities. When experimental subjects were given 100 mg/day of supplemental pyridoxine hydrochloride, tryptophan metabolism was essentially normal. These results should be considered in human metabolic studies of pyridoxine-requiring enzyme systems.^ieng

Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive.

Analogous to recommendations for treatment of side effects of early pregnancy and premenstrual syndrome, use of vitamin B6 has been recommended for the treatment of side effects of oral contraceptive (OC) use. A randomized, triple-blinded controlled trial of 124 women was done to evaluate the effect of taking 150 mg of vitamin B6 daily for 30 days on the severity of nausea, headache, vomiting, dizziness, depression, and irritability associated with the initiation of low-dose (30 micrograms norgestrel and 30 micrograms ethinyl estradiol) OG use. The severity of the symptoms was measured on a scale from 0 to 3 (not present to severe), and was evaluated at one month after admission. The two treatment groups (vitamin B, and placebo) had comparable baseline characteristics. From admission to follow up, there was a decrease in the severity of all symptoms in both groups. There was no statistically significant difference in the reductions found in the vitamin B6 and the placebo groups, although reductions in the severity of headache and dizziness were greater in the B6 group. The decrease in the severity of all OC side effects can be explained more by a placebo effect than by a marginal pharmacological effect of the vitamin B6.

PIP: Use of vitamin B-6 has been recommended for the treatment of side effects associated with combined oral contraceptive (OC) use. To evaluate this recommendation, a randomized, triple-blinded controlled trial of 124 women recruited from 2 health centers in Zacatecas, Mexico, was conducted. 62 women received 150 mg of vitamin B-6 daily for 30 days, while the remaining 62 received a placebo. All cases and controls were new or continuing users of an OC containing 30 mcg of norgestrel and 30 mcg of ethinyl estradiol. Women rated the severity of 6 common OC side effects (nausea, headache, vomiting, dizziness, depression, and irritability) on a scale from 0 to 3 at baseline and 30 days after admission. There was a decrease in the severity of all 6 symptoms in both groups. Although higher proportions of women in the vitamin B-6 group reported decreases in OC-related side effect severity between admission and the 30-day follow-up visit, these differences were appreciable only for headache and dizziness and none was statistically significant. No evidence of vitamin B-6 toxicity was observed. However, this study failed to substantiate a clinically important pharmacologic effect of vitamin B-6 on OC side effects.

[Depression, contraceptive pills and pyridoxine (vitamin B6)]. / Depresjon, P-piller og pyridoksin (vitamin B6)

PIP: Women who use oral contraceptives experience depression and loss of libido in about 7% of the cases in various studies. This may be due to a lack of pyridoxine (Vitamin-B6). Dosage of Vitamin-B6 from 20-50 mg given daily to women suffering from depression helped in many cases.^ieng

The interactions between vitamin B6 and hormones.

PIP: Vitamin-B6 interacts with both endogenous and exogenous hormones, and the data presented here concern mostly estrogens (E). E steroids compete with pyridoxal phosphate-dependent apoenzymes for the cofactor in vitro, and a similar effect probably occurs in vivo. Use of E-containing oral contraceptives was associated with an abnormality of tryptophan metabolism similar to that seen in dietary vitamin-B6 deficiency. This was corrected by pyrodoxine administration. However, plasma pyridoxal phosphate concentrations, and other indexes of vitamin-B6 nutritional status, were abnormal in only a minority of these patients. Vitamin-B6 deficiency occurred also in pregnancy,and it was proposed as at least 1 of the factors concerned in the etiology of preeclampsia. Although there was some indication that both corticosteroids and thyroid hormones increase the requirement for vitamin-B6 and modify the activiteis of pyridoxal phosphate-dependent enzymes, these relationships have received limited attention. Current work, however, reveals some interesting associations between vitamin-B6 and the regulation of anterior pituitary hormones. Mediation of these effects seems to occur at the hypothalmic level via the 2 neurotransmitters 5-hydroxytryptamine and dopamine, both of which are synthesized by vitamin-B6-dependent metabolic pathways. Potential clinical application of these results and observations is management of hyperprolactinemia, though controversy over the efficacy of pyridoxine therapy in this situation exists and remains unresolved.^ieng