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Inhibition of prolactin by pyridoxine
280
Correspondence
35:483, 1970). Too many of us use that which is advertised in the journals, not that which has been found to be most effective and proved over the years. Dr. Birnbaum mentioned the more tender pelvic organs premenstrually, when endometrial implants are so swollen and so tight that the slightest manipulation will cause pain. As mentioned before in this letter, if one administers 0.1 mg of stilbestrol daily, starting at any day of the cycle, there will be a more severe dysmenorrhea at the menstrual flow time. This is the same swelling of endometriotic lesions from small doses. If large doses of hexestrol or stilbestrol are used, these lesions are collapsed and atrophying, just the opposite to that seen when the oral contraceptives are administered. There is another test used to show that the oral contraceptives are of almost no value in endometriosis and in dysmenorrhea. The patient is taught how to insert a contraceptive applicator against the painful lesions in the pelvis, through the palpation in the vagina, or pushing the tip of the applicator against the painful area. She inserts the applicator tip against the painful lesion three times daily, and with the increasing dose of stilbestrol-Livitamin vitamins, the pains are gone by the fourth to seventh day. The ovarian atrophy is quick. On the other hand, with patients on oral contraceptives, the pains are present for 40 or more days. After the stilbestrol-vitamins are discontinued, the ovaries bounce back, a term we coined “rebound phenomenon” years ago. In passing, we had the most perfect oral contraceptive ever introduced to the medical profession-namely, stilbestrol-for over 15 years before the progestins came out. We have used this contraceptive for over 30 years, with none of the serious side reactions associated with oral contraceptives. The use of oral contraceptives in dysmenorrhea was followed for months and years, but the dysmenorrhea soon recurred. There is not enough estrogen to cause the necessary myometrial musculature to become mature enough to squeeze out the products of endometrial shedding during the menstrual flow. Many detailed “kymographic tracings” showed that dysmenorrhea was due not to increased endometrial or menstrual fluid prostaglandins, but to immature muscles in the myometrium. After stilbestrol, tetanic contractions became smooth, as seen in patients with no dysmenorrhea. Dr. Birnbaum knows that when one writes “primary dysmenorrhea” he is writing about the dysmenorrhea with no demonstrable pathology found by all means to rule out pathology, which, if found, would be labeled “secondary dysmenorrhea.” Karl John Karnahy, M.D. Director of the Obstetrical and Gynecological Research Foundation and Research Institute 2164 Addison Houston, Texas 77030
September Am. J. Obstet.
15. 1979 Gvnecol.
Inhibition of prolactin by pyricfoxine To the editors: The evidence presented in the article by Thomas J. Goodenow and William B. Malarkey (AM. J. OBSTET. GYNECOL. 133:161, 1979) that pyridoxine (vitamin B,) does not inhibit the release of the milk-producing hormone prolactin is interesting and merits comment. This finding is contrary to the numerous citations mentioned in my recent report, “Dangers of vitamin B6 in nursing mothers” (N. Engl. J. Med. 300: 141, 1979). All these sharp contradictions can reasonably be accounted for by the following: First and foremost, the powerful effects of placebos in human disease cannot be ignored. Thus, the common practice of using human models with either the galactorrhea-amenorrhea syndrome, or even cancer, about which our present ,knowledge is, unfortunately, in an embryonic stage of development, to test the effect of pyridoxine on the release of prolactin can only cause confusion at best. Second, there is now truly solid neuroendocrine evidence that vitamin Bs (pyridoxine) does indeed inhibit, at least in small mammals, the release of milkproducing prolactin.’ Third, new advances in prolactin-inhibiting hypothalamic dopamine research, and this is exciting, illustrate what the 1977 winner of the Nobel Prize in Medicine, Roger Guillemin, terms a “new endocrinology of the neuron.” The World Health Organization (WHO) and the National Research Council (NRC), the research arm of the National Academy of Science, are in sharp disagreement over the use of pyridoxine in their recommended allowance of multivitamins for children and adolescetns.2s 3 The WHO specifically and emphatically excludes vitamin B, (pyridoxine) from their recommended multivitamin formulation; the NRC takes an opposing stand. And good nutrition is a must for that particular age group. The point is made that vitamin B, deficiency rarely occurs as an isolated clinical entity as most foodstuffs contain this vitamin. In summation, after careful assessment of the risk/ benefit effects of the use of vitamin B, (pyridoxine) as presented in this correspondence it is urged, now more than ever before, that nursing mothers avoid the longterm daily use of multivitamins that have pyridoxine in their formulation. Leonard B. Greentree, M.D. 327 East State Street Columbus, Ohio 43215 REFERENCES
1. Harris, A. R. C., Smith, M. S., Alex, 8, Salhanick, H. A., Vagenakis, A. G., and Braverman, L. E.: Pvridoxine (B& induced inhibition of prolactin release in the female rat, Endocrinology 102:362, 1978. 2. Heald, F. P.T’and Roeder, L. M.: Nutrition of the school child and adolescent, in McLaren, D. S., and Burman, D., editors: Textbook of Paediatric Nutrition. New York. 1976, Churchill Livingstone, pp. 80-81.
Volume Number
Correspondence
135 2
3. World Health Organization: Handbook on Human Nutritional Requirements, Monograph series, No. 61, Geneva, 1974, World Health Organization.
Table I. Rates of low birth weight
281
for Meyer’s
study population. Birth weight under
Reply to Dr. Greentree To the Editors: We agree with Dr. Greentree that our data are contrary to those reports quoted in his “Letter to the Editors” and also detailed in our bibliography (references 7 to 10). Our findings, however, agree with those of other investigators cited in reference 13 and in the “Addendum” of our paper. At least one report that described a prolactin suppressive effect by an intravenous bolus of vitamin B, was biased by having the test begin at 8:00 A.M. when serum prolactin levels had not yet reached their nadir. As indicated in the discussion of our paper, we found a decrease in serum prolactin levels between 8:00 A.M. and 1O:OO A.M. without the administration of any agent. Thus we initiated our study of the short-term effects of vitamin B, at 1O:OO A.M. in both normal and hyperprolactinemic subjects. In regard to the effect of multivitamin preparations on puerperal lactation, Canales and associatesi reported that 450 mg of vitamin B, daily for 1 week had no effect on prolactin levels or lactation in 14 puerperal women. This contrasted with the findings of Foukas,* who noted suppression of lactation with 600 mg per day in puerperal women. In light of these observations and our findings in nonpuerperal lactation, we doubt that vitamin B, in standard multivitamin preparations, 10 mg or less per capsule, would diminish milk production in breast-feeding mothers. Finally, we share Dr. Greentree’s enthusiasm concerning dopamine-prolactin interrelationships. Thomas J. Goodenow, M.D. William B. Malarkey, M.D. Room N-1111 The Ohio State University Hospitals 410 W. 10th Avenue Columbus, Ohio 43210 REFERENCES
1. Canales, E. S., Soria, J., Zarate, A., Mason, M., and Molina, M.: The influence of pyridoxine on prolactin secretion and milk production in women, Br. J. Obstet. Gynaecol. 83: 387, 1976. 2. Foukas, M. D.: An antilactogenic effect of pyridoxine, Br. J. Obstet. Gynaeeol. 80:718, 1973.
Effects of smoking on pregnancy and newborn infants To the Editors: Since the thrust of the paper by Meyer’ is to challenge and reinterpret my2 findings, and those of Davies and associates3 I assume that you will allow a reply.
2,500
grams
(%)
Smoking level (cigarettes/day) Weight gain
C20
(Pa4
(a) (b) Ratio of (a/b) <20 20+
20+ (4
Ratio of 4.1 3.0
2.4
5.3
9.9
1.4 1.7
2.6 2.0
4.1
Cd 14
2.4
Davies and associates and I observed depressed weight gain among mothers who smoked cigarettes during pregnancy; the depressed gain was dose-related and in both studies statistically accounted for most of the effects of smoking on birth weight. Meyer asserts she has not observed depressed weight gain with smoking; however, she does not present the distribution of maternal weight gain by smoking (her Fig. 2) separately for light and moderate smokers (who cannot be distinguished in her data) and heavy smokers (over one pack daily). Since the effect on light smokers that we observed is weak, a strong effect on the smaller number of heavy smokers might thus be obscured in Meyer’s data. Further, Kass and I,4 on reviewing the English language literature, found an intense interaction of social status with smoking related to the potential lethality in the fetus: Upper-status smokers protect their fetuses from the effects of smoking whereas lower-status smokers do not. We now have evidence that this partial protection is likely mediated by a sustained weight gain in pregnancy. Indeed, Spira and Servent,s in their study of a group of French women, did not observe a depressed weight gain among light (
Correspondence
35:483, 1970). Too many of us use that which is advertised in the journals, not that which has been found to be most effective and proved over the years. Dr. Birnbaum mentioned the more tender pelvic organs premenstrually, when endometrial implants are so swollen and so tight that the slightest manipulation will cause pain. As mentioned before in this letter, if one administers 0.1 mg of stilbestrol daily, starting at any day of the cycle, there will be a more severe dysmenorrhea at the menstrual flow time. This is the same swelling of endometriotic lesions from small doses. If large doses of hexestrol or stilbestrol are used, these lesions are collapsed and atrophying, just the opposite to that seen when the oral contraceptives are administered. There is another test used to show that the oral contraceptives are of almost no value in endometriosis and in dysmenorrhea. The patient is taught how to insert a contraceptive applicator against the painful lesions in the pelvis, through the palpation in the vagina, or pushing the tip of the applicator against the painful area. She inserts the applicator tip against the painful lesion three times daily, and with the increasing dose of stilbestrol-Livitamin vitamins, the pains are gone by the fourth to seventh day. The ovarian atrophy is quick. On the other hand, with patients on oral contraceptives, the pains are present for 40 or more days. After the stilbestrol-vitamins are discontinued, the ovaries bounce back, a term we coined “rebound phenomenon” years ago. In passing, we had the most perfect oral contraceptive ever introduced to the medical profession-namely, stilbestrol-for over 15 years before the progestins came out. We have used this contraceptive for over 30 years, with none of the serious side reactions associated with oral contraceptives. The use of oral contraceptives in dysmenorrhea was followed for months and years, but the dysmenorrhea soon recurred. There is not enough estrogen to cause the necessary myometrial musculature to become mature enough to squeeze out the products of endometrial shedding during the menstrual flow. Many detailed “kymographic tracings” showed that dysmenorrhea was due not to increased endometrial or menstrual fluid prostaglandins, but to immature muscles in the myometrium. After stilbestrol, tetanic contractions became smooth, as seen in patients with no dysmenorrhea. Dr. Birnbaum knows that when one writes “primary dysmenorrhea” he is writing about the dysmenorrhea with no demonstrable pathology found by all means to rule out pathology, which, if found, would be labeled “secondary dysmenorrhea.” Karl John Karnahy, M.D. Director of the Obstetrical and Gynecological Research Foundation and Research Institute 2164 Addison Houston, Texas 77030
September Am. J. Obstet.
15. 1979 Gvnecol.
Inhibition of prolactin by pyricfoxine To the editors: The evidence presented in the article by Thomas J. Goodenow and William B. Malarkey (AM. J. OBSTET. GYNECOL. 133:161, 1979) that pyridoxine (vitamin B,) does not inhibit the release of the milk-producing hormone prolactin is interesting and merits comment. This finding is contrary to the numerous citations mentioned in my recent report, “Dangers of vitamin B6 in nursing mothers” (N. Engl. J. Med. 300: 141, 1979). All these sharp contradictions can reasonably be accounted for by the following: First and foremost, the powerful effects of placebos in human disease cannot be ignored. Thus, the common practice of using human models with either the galactorrhea-amenorrhea syndrome, or even cancer, about which our present ,knowledge is, unfortunately, in an embryonic stage of development, to test the effect of pyridoxine on the release of prolactin can only cause confusion at best. Second, there is now truly solid neuroendocrine evidence that vitamin Bs (pyridoxine) does indeed inhibit, at least in small mammals, the release of milkproducing prolactin.’ Third, new advances in prolactin-inhibiting hypothalamic dopamine research, and this is exciting, illustrate what the 1977 winner of the Nobel Prize in Medicine, Roger Guillemin, terms a “new endocrinology of the neuron.” The World Health Organization (WHO) and the National Research Council (NRC), the research arm of the National Academy of Science, are in sharp disagreement over the use of pyridoxine in their recommended allowance of multivitamins for children and adolescetns.2s 3 The WHO specifically and emphatically excludes vitamin B, (pyridoxine) from their recommended multivitamin formulation; the NRC takes an opposing stand. And good nutrition is a must for that particular age group. The point is made that vitamin B, deficiency rarely occurs as an isolated clinical entity as most foodstuffs contain this vitamin. In summation, after careful assessment of the risk/ benefit effects of the use of vitamin B, (pyridoxine) as presented in this correspondence it is urged, now more than ever before, that nursing mothers avoid the longterm daily use of multivitamins that have pyridoxine in their formulation. Leonard B. Greentree, M.D. 327 East State Street Columbus, Ohio 43215 REFERENCES
1. Harris, A. R. C., Smith, M. S., Alex, 8, Salhanick, H. A., Vagenakis, A. G., and Braverman, L. E.: Pvridoxine (B& induced inhibition of prolactin release in the female rat, Endocrinology 102:362, 1978. 2. Heald, F. P.T’and Roeder, L. M.: Nutrition of the school child and adolescent, in McLaren, D. S., and Burman, D., editors: Textbook of Paediatric Nutrition. New York. 1976, Churchill Livingstone, pp. 80-81.
Volume Number
Correspondence
135 2
3. World Health Organization: Handbook on Human Nutritional Requirements, Monograph series, No. 61, Geneva, 1974, World Health Organization.
Table I. Rates of low birth weight
281
for Meyer’s
study population. Birth weight under
Reply to Dr. Greentree To the Editors: We agree with Dr. Greentree that our data are contrary to those reports quoted in his “Letter to the Editors” and also detailed in our bibliography (references 7 to 10). Our findings, however, agree with those of other investigators cited in reference 13 and in the “Addendum” of our paper. At least one report that described a prolactin suppressive effect by an intravenous bolus of vitamin B, was biased by having the test begin at 8:00 A.M. when serum prolactin levels had not yet reached their nadir. As indicated in the discussion of our paper, we found a decrease in serum prolactin levels between 8:00 A.M. and 1O:OO A.M. without the administration of any agent. Thus we initiated our study of the short-term effects of vitamin B, at 1O:OO A.M. in both normal and hyperprolactinemic subjects. In regard to the effect of multivitamin preparations on puerperal lactation, Canales and associatesi reported that 450 mg of vitamin B, daily for 1 week had no effect on prolactin levels or lactation in 14 puerperal women. This contrasted with the findings of Foukas,* who noted suppression of lactation with 600 mg per day in puerperal women. In light of these observations and our findings in nonpuerperal lactation, we doubt that vitamin B, in standard multivitamin preparations, 10 mg or less per capsule, would diminish milk production in breast-feeding mothers. Finally, we share Dr. Greentree’s enthusiasm concerning dopamine-prolactin interrelationships. Thomas J. Goodenow, M.D. William B. Malarkey, M.D. Room N-1111 The Ohio State University Hospitals 410 W. 10th Avenue Columbus, Ohio 43210 REFERENCES
1. Canales, E. S., Soria, J., Zarate, A., Mason, M., and Molina, M.: The influence of pyridoxine on prolactin secretion and milk production in women, Br. J. Obstet. Gynaecol. 83: 387, 1976. 2. Foukas, M. D.: An antilactogenic effect of pyridoxine, Br. J. Obstet. Gynaeeol. 80:718, 1973.
Effects of smoking on pregnancy and newborn infants To the Editors: Since the thrust of the paper by Meyer’ is to challenge and reinterpret my2 findings, and those of Davies and associates3 I assume that you will allow a reply.
2,500
grams
(%)
Smoking level (cigarettes/day) Weight gain
C20
(Pa4
(a) (b) Ratio of (a/b) <20 20+
20+ (4
Ratio of 4.1 3.0
2.4
5.3
9.9
1.4 1.7
2.6 2.0
4.1
Cd 14
2.4
Davies and associates and I observed depressed weight gain among mothers who smoked cigarettes during pregnancy; the depressed gain was dose-related and in both studies statistically accounted for most of the effects of smoking on birth weight. Meyer asserts she has not observed depressed weight gain with smoking; however, she does not present the distribution of maternal weight gain by smoking (her Fig. 2) separately for light and moderate smokers (who cannot be distinguished in her data) and heavy smokers (over one pack daily). Since the effect on light smokers that we observed is weak, a strong effect on the smaller number of heavy smokers might thus be obscured in Meyer’s data. Further, Kass and I,4 on reviewing the English language literature, found an intense interaction of social status with smoking related to the potential lethality in the fetus: Upper-status smokers protect their fetuses from the effects of smoking whereas lower-status smokers do not. We now have evidence that this partial protection is likely mediated by a sustained weight gain in pregnancy. Indeed, Spira and Servent,s in their study of a group of French women, did not observe a depressed weight gain among light (