1126 EFFECT OF ZINC ADMINSTRATION ON SERUM-ZINC, PLASMA-TESTOSTERONE AND SPERM-COUNT: MEAN ± S.E.M.
These findings seem to be confirmed by fifteen more cases but the data are incomplete. The wife of one patient became pregnant after her husband had taken zinc sulphate for 6 weeks. Serum-zinc concentrations depend upon nutritional factors 2-1 geological environment,6 and, probably, other factors Plasma-testosterone is related to serum-zinc only in men over 36 years of age.7 Zinc plays an important role in prostatic, epididymal, and testicular function,2,4.8-11but the relationship between oligospermia and zinc has not yet been studied. Our findings seem to open a new prospect for the treatment of some cases of oligospermia of unknown origin.
Oulu, Finland
T. RIITA HARTOMA
Foundation de Recherche
K. NAHOUL A. NETTER
Hormonologie,
94260 - Fresnes, France
FERTILISATION IN WOMEN WITH INTRAUTERINE DEVICES
SIR,-Landesman et al.12 and Beling et al.," using a radioiman antiserum specific to the [3-subunit of gonadotrophin (H.C.G.), have detected circulating H.C.G. during the luteal phase in women fitted with an intrauterine device (L U .D.). They regard this as a sign of fertilisation, implying that l.U.D.s act by interfering with implantation rather than by inhibiting fertilisation. Landesman et al. detected H.C.G. in 12-19% of LU.D. users as early as 5-7 days after the predicted ovulatory luteinising-hormone (L.H.) surge. Beling et al. found H.C.G. in 3 out of 30 I.U.D. users (10%) but not until 10-13 days after the postulated ovulation. Beling et al. also reported a rise of H.C.G. in two cycles during which fertilisation occurred and normal pregnancies ensued; this rise did not occur until 10 days after a registered ovulatory L.H. surge. In an i.u.D. user the same rise occurred 12 days after a detected ovulatory L.H.-peak. We have studied 55 I.U.D. users (’CuT-200’) and found only 1 with detectable H.C.G. concentrations. Blood-samples were taken 10-15 days after the predicted ovulatory L.H. surge from women with a history of regular menstrual cycles of between 24 and 32 days. 2 unprotected patients who became pregnant were also monitored by determination of L.H. and H.C.G. from plasma samples obtained three times weekly. In both pregnancies the H.C.G. did not rise until the 12th day after the detected
munoassay with human chorionic
ovulatory L.H. surge. We feel that a radioimmunoassay specific
for the
p-subunit
2. 3. 4. 5.
Vallee, B. L. Physiol. Rev. 1959, 39, 443. Halsted, J. A., Smith, J. C. Lancet, 1970, i, 322. Prasad, A. S., Halsted, J. A., Nadimi, M. Am. J. Med. 1961, 31, 532. Hartoma, T. R., Sotaniemi, E. A., Pelkonen, O., Ahlqvist, J. Eur. J. clin. Pharmac. 1977, 12, 1. 6. Hartoma, T. R. Unpublished. 7. Hartoma, T. R. Acta physiol. scand. 1977, 100, 1. 8. Bertrand, G. C. r. Acad. Sci. 1920,171, 176. 9. Mawson, C. A., Fischer, M. I. Can. J. med. Sci. 1952, 30, 336. 10. Eliasson, R., Lindholmer, C. Andrologie, 1971, 3, 146. 11. Wallace, A. M., Grant, J. K. Biochem. Soc. Trans. 1975, 3, 540. 12. Landesman, R., Coutinho, E. M., Saxena, B. B. Fertil. Steril. 1976, 27, 13.
1062. C. 855.
Beling,
will not detect significantly increased amounts of in plasma until 9-10 days after the midcycle L.H. peak, and thus presumably not until implantation has already happened. The finding of Landesman et al. of H.C.G. in plasma as early as 5 days after a predicted ovulation seems to be uncertain, due to the unknown temporal relation between sampling and ovulation and subsequent menstruation. The late luteal phase peaking of L.H. cannot be ruled out in a H.C.G. radioreceptor assay. Landesman et al. do not give any reference values for their H.c.G. radioimmunoassay, and in no instance was the rise in plasma-H.c.G. more than threefold. In our single positive H.c.G. sample, recorded in a woman who was monitored by measurements done three times weekly, we found a 10-fold rise from the basal values of the assay used. Furthermore Groom has reportedI4 measurable amounts of the p-subunit of H.C.G. in 11% of random home-collected bloodsamples. Thus a small rise in H.c.G., measured with a specific radioimmunoassay for the 3-subunit in a single sample obtained during a luteal phase, is not a sure sign of conception. More careful monitoring of larger series of l.u.D. users must be done before we can decide if the I.V.D. is abortifacient. The frequency of "early abortions" should also be studied in cycles of H.C.G.
H.c.G.
unprotected women. Steroid Research Laboratory, Department of Medical Chemistry,
Department of Physiology, University of Oulu,
en
of
University of Helsinki, SF-00170 Helsinki 17, Finland
C. G. NILSSON P. LÄHTEENMÄKI
FLOPPY-INFANT SYNDROME: IS OXAZEPAM THE ANSWER?
SIR,-Dr Gillberg (July 30, p. 244) has suggested that oxazepam in pre-eclampsia might be safer for the newborn infant than is diazepam. Oxazepam has been used in this way at Redhill General Hospital since March, and so far all infants have been born in good condition. A double-blind trial with diazepam did not seem justified, since diazepam has affected our babies in the past and similar findings have been recorded by others. 1-5 one of the metabolites of diazepam. Because it short half-life6-8 and no known biologically active metabolites, it might be expected to be the safer drug. We have investigated the value of oxazepam in pre-eclampsia by clinical findings and measurement of plasma and urine drug concentrations. Small divided doses of 30-45 mg daily were prescribed without any adverse effects on the babies. Subsequently 75 mg daily has been used successfully in six pregnancies. Maternal and cord blood samples were taken and the Apgar scores were recorded. In the infants urinary excretions of free and conjugated oxazepam were measured within the first 24 h and the plasma concentrations of oxazepam were determined at 24 and 48 h. Oxazepam crossed the placenta and at the time of delivery concentrations were usually higher in cord blood than maternal blood. No case of "floppy infant" syndrome has been encountered in thirty pregnancies managed in this way. Oxazepam is of limited use in pre-eclampsia because no parenteral formulation is available. However, patients tolerate the drug well and are not unduly drowsy. Urinary oestrogen con-
Oxazepam is
has
a
14. Groom, G. V. J. Reprod. Fertil. 1977, 51, 273. 1. Shannon, R. W., Fraser, G. P., Aitken, R. G., Harper, J. R. Br. J. clin. Pract. 1972, 26, 271. 2. Scher, J., Hailey, D. M., Beard, R. W. J. Obstet. Gynœc. Br. Commonw.
1972, 79, 635. Kanto, J., Errkola, R. Ann. Chir. Gynœc. fenn. 1974, 63, 489. Cree, J. E., Meyer, J., Hailey, D. M. Br. med. J. 1973, iv, 251. Gamble, J. A. S., Moore, J., Lamki, H., Howard, P. J. Br. J. Obstet. Gynœc. 1977, 84, 588. 6. Vessman, J., Alexanderson, B., Sjöqvist, F., Strindberg, B., Sundwall, A. in The Benzodiazepines (edited by S. Garattini, E. Mussini, and L. O. Randall); p. 165. New York, 1973. 7. Wretlind, M., Pilbrant, A., Sundwall, A., Vessman, J. Acta pharmac. toxi3. 4. 5.
G., Cederquist, L. L., Fuchs, F. Am. J. Obstet. Gynec. 1976, 125,
col., 1977, 40, suppl. 1, p. 28. 8.
Alvan, G., Siwers, B., Vessman, J. ibid. p. 40.
These findings seem to be confirmed by fifteen more cases but the data are incomplete. The wife of one patient became pregnant after her husband had taken zinc sulphate for 6 weeks. Serum-zinc concentrations depend upon nutritional factors 2-1 geological environment,6 and, probably, other factors Plasma-testosterone is related to serum-zinc only in men over 36 years of age.7 Zinc plays an important role in prostatic, epididymal, and testicular function,2,4.8-11but the relationship between oligospermia and zinc has not yet been studied. Our findings seem to open a new prospect for the treatment of some cases of oligospermia of unknown origin.
Oulu, Finland
T. RIITA HARTOMA
Foundation de Recherche
K. NAHOUL A. NETTER
Hormonologie,
94260 - Fresnes, France
FERTILISATION IN WOMEN WITH INTRAUTERINE DEVICES
SIR,-Landesman et al.12 and Beling et al.," using a radioiman antiserum specific to the [3-subunit of gonadotrophin (H.C.G.), have detected circulating H.C.G. during the luteal phase in women fitted with an intrauterine device (L U .D.). They regard this as a sign of fertilisation, implying that l.U.D.s act by interfering with implantation rather than by inhibiting fertilisation. Landesman et al. detected H.C.G. in 12-19% of LU.D. users as early as 5-7 days after the predicted ovulatory luteinising-hormone (L.H.) surge. Beling et al. found H.C.G. in 3 out of 30 I.U.D. users (10%) but not until 10-13 days after the postulated ovulation. Beling et al. also reported a rise of H.C.G. in two cycles during which fertilisation occurred and normal pregnancies ensued; this rise did not occur until 10 days after a registered ovulatory L.H. surge. In an i.u.D. user the same rise occurred 12 days after a detected ovulatory L.H.-peak. We have studied 55 I.U.D. users (’CuT-200’) and found only 1 with detectable H.C.G. concentrations. Blood-samples were taken 10-15 days after the predicted ovulatory L.H. surge from women with a history of regular menstrual cycles of between 24 and 32 days. 2 unprotected patients who became pregnant were also monitored by determination of L.H. and H.C.G. from plasma samples obtained three times weekly. In both pregnancies the H.C.G. did not rise until the 12th day after the detected
munoassay with human chorionic
ovulatory L.H. surge. We feel that a radioimmunoassay specific
for the
p-subunit
2. 3. 4. 5.
Vallee, B. L. Physiol. Rev. 1959, 39, 443. Halsted, J. A., Smith, J. C. Lancet, 1970, i, 322. Prasad, A. S., Halsted, J. A., Nadimi, M. Am. J. Med. 1961, 31, 532. Hartoma, T. R., Sotaniemi, E. A., Pelkonen, O., Ahlqvist, J. Eur. J. clin. Pharmac. 1977, 12, 1. 6. Hartoma, T. R. Unpublished. 7. Hartoma, T. R. Acta physiol. scand. 1977, 100, 1. 8. Bertrand, G. C. r. Acad. Sci. 1920,171, 176. 9. Mawson, C. A., Fischer, M. I. Can. J. med. Sci. 1952, 30, 336. 10. Eliasson, R., Lindholmer, C. Andrologie, 1971, 3, 146. 11. Wallace, A. M., Grant, J. K. Biochem. Soc. Trans. 1975, 3, 540. 12. Landesman, R., Coutinho, E. M., Saxena, B. B. Fertil. Steril. 1976, 27, 13.
1062. C. 855.
Beling,
will not detect significantly increased amounts of in plasma until 9-10 days after the midcycle L.H. peak, and thus presumably not until implantation has already happened. The finding of Landesman et al. of H.C.G. in plasma as early as 5 days after a predicted ovulation seems to be uncertain, due to the unknown temporal relation between sampling and ovulation and subsequent menstruation. The late luteal phase peaking of L.H. cannot be ruled out in a H.C.G. radioreceptor assay. Landesman et al. do not give any reference values for their H.c.G. radioimmunoassay, and in no instance was the rise in plasma-H.c.G. more than threefold. In our single positive H.c.G. sample, recorded in a woman who was monitored by measurements done three times weekly, we found a 10-fold rise from the basal values of the assay used. Furthermore Groom has reportedI4 measurable amounts of the p-subunit of H.C.G. in 11% of random home-collected bloodsamples. Thus a small rise in H.c.G., measured with a specific radioimmunoassay for the 3-subunit in a single sample obtained during a luteal phase, is not a sure sign of conception. More careful monitoring of larger series of l.u.D. users must be done before we can decide if the I.V.D. is abortifacient. The frequency of "early abortions" should also be studied in cycles of H.C.G.
H.c.G.
unprotected women. Steroid Research Laboratory, Department of Medical Chemistry,
Department of Physiology, University of Oulu,
en
of
University of Helsinki, SF-00170 Helsinki 17, Finland
C. G. NILSSON P. LÄHTEENMÄKI
FLOPPY-INFANT SYNDROME: IS OXAZEPAM THE ANSWER?
SIR,-Dr Gillberg (July 30, p. 244) has suggested that oxazepam in pre-eclampsia might be safer for the newborn infant than is diazepam. Oxazepam has been used in this way at Redhill General Hospital since March, and so far all infants have been born in good condition. A double-blind trial with diazepam did not seem justified, since diazepam has affected our babies in the past and similar findings have been recorded by others. 1-5 one of the metabolites of diazepam. Because it short half-life6-8 and no known biologically active metabolites, it might be expected to be the safer drug. We have investigated the value of oxazepam in pre-eclampsia by clinical findings and measurement of plasma and urine drug concentrations. Small divided doses of 30-45 mg daily were prescribed without any adverse effects on the babies. Subsequently 75 mg daily has been used successfully in six pregnancies. Maternal and cord blood samples were taken and the Apgar scores were recorded. In the infants urinary excretions of free and conjugated oxazepam were measured within the first 24 h and the plasma concentrations of oxazepam were determined at 24 and 48 h. Oxazepam crossed the placenta and at the time of delivery concentrations were usually higher in cord blood than maternal blood. No case of "floppy infant" syndrome has been encountered in thirty pregnancies managed in this way. Oxazepam is of limited use in pre-eclampsia because no parenteral formulation is available. However, patients tolerate the drug well and are not unduly drowsy. Urinary oestrogen con-
Oxazepam is
has
a
14. Groom, G. V. J. Reprod. Fertil. 1977, 51, 273. 1. Shannon, R. W., Fraser, G. P., Aitken, R. G., Harper, J. R. Br. J. clin. Pract. 1972, 26, 271. 2. Scher, J., Hailey, D. M., Beard, R. W. J. Obstet. Gynœc. Br. Commonw.
1972, 79, 635. Kanto, J., Errkola, R. Ann. Chir. Gynœc. fenn. 1974, 63, 489. Cree, J. E., Meyer, J., Hailey, D. M. Br. med. J. 1973, iv, 251. Gamble, J. A. S., Moore, J., Lamki, H., Howard, P. J. Br. J. Obstet. Gynœc. 1977, 84, 588. 6. Vessman, J., Alexanderson, B., Sjöqvist, F., Strindberg, B., Sundwall, A. in The Benzodiazepines (edited by S. Garattini, E. Mussini, and L. O. Randall); p. 165. New York, 1973. 7. Wretlind, M., Pilbrant, A., Sundwall, A., Vessman, J. Acta pharmac. toxi3. 4. 5.
G., Cederquist, L. L., Fuchs, F. Am. J. Obstet. Gynec. 1976, 125,
col., 1977, 40, suppl. 1, p. 28. 8.
Alvan, G., Siwers, B., Vessman, J. ibid. p. 40.
