Pregnancy hormone concentrations in marijuana users

Pergamon Press

Life Sciences, Vol. 33, pp. 195-199 Printed in the U.S.A.

PREGNANCY Glenn Departments

HORMONE

D. Braunstein, of Medicine,

Center,

CONCENTRATIONS

John E. Buster, Obstetrics

UCLA

IN MARIJUANA

James R. Soares and Stanley

and Gynecology,

School of Medicine,

USERS

and Anatomy,

Los Angeles,

(Received in final form May 2,

California

J. Gross

Cedars-Sinai

Medical

90048.

1983)

Summary The maternal serum concentrations of human chorionic gonadotropin, pregnancy-specific beta- I -glycoprotein, placental lactogen, progesterone, l7-hydroxyprogesterone, estradiol and estriol were measured in I3 women who smoked marijuana regularly throughout pregnancy. Cannabinoid use in these women was confirmed by RIA measurements of their serum A 9tetrahydrocannabinol (THC) concentrations. These THC using women were matched within 2 l/2 weeks of gestational age with I3 pregnant non-THC using controls drawn from the same population. Placental protein and steroid hormone concentrations were within established normal ranges for gestational age and there were no significant differences between the groups in the concentrations of any of the protein and steroids measured. In addition, no significant differences between THC users were found following linear regression analysis of placental hormone concentrations as a function of gestational age. Thus, this study suggests that marijuana use during pregnancy does not significantly alter the circulating maternal concentrations of trophoblastic protein hormones or major fetoplacental steroid hormones. Although a number of investigators have studied the effects of marijuana on pregnancy and offspring in rodents and subhuman primates (I), there is little information available concerning the effects of marijuana use during human gestation. Based on animal studies, it has been postulated that marijuana use may interfere with normal placental function (2). Since maternal serum concentrations of placental trophoblastic proteins and fetoplacental steroids are useful clinical indices of pregnancy status, we measured several such pregnancy related protein and steroid hormones in the blood of women who smoked marijuana during pregnancy and compared their concentrations to a control group of non-marijuana using pregnant women drawn from the same population. Subjects

and Methods

Thirteen women who regularly smoked marijuana during their pregnancy but did not use other illicit drugs within 3 months of conception or during pregnancy were recruited for this study (THC group). Marijuana use by these subjects varied and the range of reported frequency of “getting stoned” varied from once per month to 4 times a da Marijuana use in each of these patients was confirmed by serum measurements of A 4. tetrahydrocannabinol (THC) performed by radioimmunoassay (31, and serum concentrations varied between 3.2 and 70.6 ng/ml indicating marijuana use within two to four These patients were matched within two weeks of hours prior to venipuncture (4). gestational age with women drawn from the same clinic population who did not use illegal drugs during pregnancy or the three months prior to mari juana or other conception. None of the control patients had measurable quantities of A 9-THC or or urine 9-substituted tetrahydrocannabinol, a measurable quantities of serum 0024-3205183

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Copyright (c) 1983 Pergamon Press Ltd.

Pregnancy

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metabolite that may be detected in the urine for two weeks following marijuana use (4). Urine screens (Abuscreen radioimmunoassay, Roche Diagnostics, Nutley, NJ) for morphine, cocaine, amphetamine, barbiturates and phencyclidine were performed on all patients and none of these substances were detected. Gestational length was determined by assessment of the patient’s last menstrual period, the date of delivery, and the gestational age of the offspring as determined by the examining pediatrician. The mean gestational length was 20.5 weeks in the control group and 20.9 weeks in the THC group (N.S. by paired t-test). There was an even distribution of pregnant women over the length of gestation in both groups, ranging from Il.5 to 37 weeks of gestational age (first trimester, 5 control, 4 THC; second trimester, 5 control, 5 THC; third trimester, 3 control, 4 THC). Single blood samples were obtained from each of the patients and controls, the serum separated and the samples stored until assay. Each assay, including THC, was performed on every sample. Serum concentrations of human chorionic gonadotropin (hCG), pregnancy-specific beta- I-glycoprotein (SP I, PS f3G), human placental lactogen (hPL), progesterone (PI, I7hydroxyprogesterone (I 70HP), estradiol I7 f3 (E2), and estriol (E3) were measured by previously described rodioimmunoassays (5-7). The results from each subject were compared with the normal ranges for duration of pregnancy previously established for these proteins and hormones (5-8). Since subjects in the THC and control groups were matched with respect to gestational age, differences in serum steroid hormone and trophoblastic protein concentrations between the two groups were analyzed by the Wilcoxon Matched-Pairs Signed-Ranks Test, a nonparametric technique (9). Differences between the two groups in serum protein and steroid hormone concentrations were also assessed by Student’s paired t-test following logarithmic transformation of the data. The relationships between gestational age and hormone concentrations were determined by fitting a separate linear least squares regression line to the hormone concentrations and pregnancy duration for each group. The resulting slopes and intercepts for both groups were statistically tested by an analysis of variance technique (IO). The qualitative curve of hCG secretion during pregnancy, with a first trimester peak and lower concentrations during the second and third trimesters (5), precluded us from performing a meaningful linear regression analysis for this hormone. Significant differences for all statistical tests were considered to be present when ~(0.05 (two-tailed). Results All placental protein and steroid hormone levels in each group were within the The median concentrations during established normal ranges for gestational age (5-8). each trimester are given in Table I. TABLE MEDIAN MATERNAL SERUM PROTEINS AND STEROID hCG FIRST

CONCENTRATIONS HORMONES (ng/ml)

SPI

hPL -

I8350 I5205

434 279

26.4 23.2

1.4 I.1

:::

co.2 CO.2

32000 33800

I726 I345

42.9 35.5

2.0 1.6

6.0 5.5

I:;

I64500 121500

3894 3856

96.2 90.4

3.6 2.3

13.2 IO.6

10.5 5.8

-

P

OF PREGNANCY BY TRIMESTER l70HP

5

&I

TRIMESTER

Control THC SECOND

I4760 12100

TRIMESTER

Control THC THIRD

I

2800 2700

TRIMESTER

Control THC

I394 4900

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There were no significant differences between the THC and control groups for any protein or steroid hormone level by the non-parametric analysis. Figure I illustrates the mean (following logarithmic transformation) and 95% confidence limits for each of the proteins and steroids measured in all of the serum samples obtained from the two groups. Again, no significant differences in hormone concentrations were found between the THC and control groups. The linear regression lines fitted for hormone concentrations as a function of advancing gestational age were not significantly different between groups. There was no correlation between serum THC levels and any of the hormones measured in the THC group.

hCG 10000,

T

hPL _

CONTROL HTHC

10

17-OHP

E3

10

1 5.0

5.0

1

T

T

FIG. I Logarithmic normalized mean concentrations of trophoblastic proteins and steroid hormone concentrations in maternal serum of control patients and patients who used marijuana (THC) throughout pregnancy. Bars represent 95% confidence limits of the mean. Differences between the two groups of patients were not significant. Discussion The effects of marijuana on human reproduction are controversial with divergent results emanating from different laboratories (I). However, there is evidence that two constituents of marijuana, A Y-THC and cannabinol, as well as smoked marijuana condensate, possess antiandrogenic effects, and competitively inhibit the binding of dih drotestosterone to the androgen receptor present in rat ventral prostate cytosol (I I). A 4 -THC has been shown to be capable of displacing androgens from the cytosol androgen receptor in human term placenta (12). In addition, AY-THC and possibly other constituents of marijuana appear to have estrogenic activity in some -in vivo and in vitro test systems (I 3- 151, and THC administration suppresses pituitary gonadotropinrelease in rhesus monkeys (16). Since there is evidence suggesting that both hCG

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and hPL production may be modulated by the concentration of circulating sex steroid hormones (I 7, 18), it might have been anticipated that the maternal serum concentrations of these trophoblastic protein hormones would have been altered in the group of patients who used marijuana. Similarly, it might have been expected that a substance possessing steroid bioactivity may alter the placental contribution to circulating sex steroid hormone concentrations (19). However, the results of our study suggest that marijuana use during pregnancy does not significantly alter the maternal levels of placental trophoblastic protein hormones or the major steroid hormones derived from Since the serum concentrations of these maternal sources or the fetoplacental unit. substances were unchanged, it is unlikely that THC use alters the production or clearance of these proteins and steroid hormones. The women in our THC group were selected on the basis of their history of Although each of the subjects in marijuana use and the presence of THC in their blood. the THC group used marijuana regularly, the variable degree of use and the small sample size precludes us from drawing firm conclusions about the effects of chronic, high-dose marijuana use during pregnancy. In addition, the possibility of preconception adaptive tolerance to THC in our patients prevents extrapolation of the results of our study to individuals who smoke marijuana for the first time during pregnancy. The normal maternal serum concentrations of placental protein and steroid hormones in each of the individual patients studied is consistent with prior studies that have failed to demonstrate major teratogenic effects of marijuana in primates (I, 20-22). However, we do not wish to imply that marijuana does not affect either the pregnancy or the fetus. Marijuana use during pregnancy has been associated with a significant decrease in fetal birth weight, an increase in the duration of labor, increased risk for intrapartum passage of meconium by the fetus, significant short-term alterations in neonatal central nervous system activity and increased risk for the development of features compatible with the fetal alcohol syndrome (23-25). Acknowledgements

Ms. from

The assistance of Dr. Sander Greenland, Ms. Nancy Brown, Ms. Moraye Bear and Joan Rasor is gratefully appreciated. This work was supported in part by a grant the National Institutes on Drug Abuse (5 RO I DA 02 132). References

I. 2.

3. 4. 5. 6.

7.

8.

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