Precocious sexual development in Puerto Rico, linked to DES, 1982
“Your editorial of March 27 on the use of anabolic steroids in the meat production was of great interest to us. We are very worried about this practice: it has been allowed by the World Health Organisation but the necessary controls will not be strictly enforced in many countries. In Puerto Rico products such as diethylstilboestrol (DES) and zeranol are sold over the counter without a veterinary prescription. We have been investigating this matter because of an alarming incidence of premature telarche in Puerto Rico.”
NCBI PubMed Anabolic steroids in meat and premature telarchePMID: 6123033 and Precocious sexual development in Puerto RicoPMID: 6123032, 1982.
From previous studies carried out in the Istituto Superiore di Sanità, Roma over the years 1979-1980, it was hypothesized that calf meat-derived, homogenized and lyophilized baby food might contain high doses of compounds endowed with oestrogenic actiuity.
Thus, analytical investigations performed on 450 samples of commercial baby-food products, showed that 150 of them contained a powerful oestrogenic substance, later on identified as diethylstilbestrol (DES), in high amount (20 to 140 ug/kg food).
Since meat from calves illegally treated with xenobiotic drugs having hormonal activity generally contains modest yet potentially dangerous levels of such compounds (in the range 0.1 to 2 ug/kg meat), it was derived that the elevated DES levels in homogenized products could be originated from working plout or injectable preparation DES residues, given to animals as auxin.
Similar considerations are advanced to explain the etiopathogenesis of gynoecomastia, early pseudopuberty, or troubles in the sex organs of school-age children described in Italy as well as in other countries during these later years.
The case of diethylstilbestrol treated veal contained in homogenized baby-foods in Italy. Methodological and toxicological aspects, Annali dell’Istituto superiore di sanita, NCBI PubMed PMID: 6549589, 1984.
In-utero exposure to DES results in incomplete gonadal development and, consequently, smaller testes and lower testosterone levels, 1983
A group of boys exposed to diethylstilbestrol (DES) in utero who had earlier been found to have urogenital abnormalities were studied for evidence of later effects of DES on their health, physical development and hormonal status. They showed no difference in age at onset of puberty, development of sexual characteristics or hormone levels from boys of the same age who had not been exposed to DES. However, the exposed group tended to have smaller testes.
A group of 15 boys exposed to diethylstilbestrol (DES) in utero who had earlier been found to have urogenital abnormalities and 25 controls participated in a comparative study of age of onset of puberty and of postpubertal hormone levels. The mean ages of the 2 groups were 15.1 and 15.8 years respectively. 4 criteria were used to determine onset of puberty: development of pubic hair, change of voice, shaving of facial hair, and onset of ejaculation. 60% of both the exposed group and control group fulfilled 3 of 4 criteria for the onset of puberty and were thus consider postpubertal. Median ages of onset of puberty determined from interviews were 13.9 for the exposed group and 13.8 for the control group. Mean heights of the prepubertal boys were 230.9 and 234.8 cm respectively and mean weights were 45.0 and 45.9 kg. Mean heights were also similar in the postpubertal group, at 278.2 and 280.9 cm, but mean weight of 69.5 in the exposed group was lower than the 76.8 kg of the control group was unremarkable. No substantial differences were detected in the geometric mean hormone levels of the 2 groups. However, postpubertal boys in the exposed group had significantly smaller testes: in 7 of 8 exposed boys but only 6 of 15 control subjects the testes were less than 3000 square millimeters in area. 1 exposed boy refused this part of the examination. 14 of the 15 exposed boys were currently asymptomatic with respect to their previous urogenital problems and 1 had persistent enuresis.
Effect of in-utero exposure to diethylstilbestrol on age at onset of puberty and on postpubertal hormone levels in boys, Canadian Medical Association journal, NCBI PubMed PMC1875289, 1983.
DES linked to feminization in boys and precocious puberty in girls
This paper reviews both minor and major adverse reactions caused by estrogenic substances (natural and synthetic, steroidal and nonsteroidal) of which diethylstilbestrol is the prototype of nonsteroidal synthetic estrogen.
Minor side effects include nausea, breast tenderness, and excessive cervical secretions (most common), headache, and water and salt retention (less common and often eradicated by lowering estrogen dosage). Vertigo, yeast infections, depression, and photosensitivity are other minor effects.
Major effects include those on the endocrine system (e.g., feminization in boys and men and precocious puberty in girls); breast tumors; endometrial carcinoma; ovarian tumors; hypertension; thromboembolism; blood clotting excesses; various metabolic effects (including lipid metabolism and carbohydrate metabolism alterations); liver changes (bile alterations and neoplasms); porphyria; melanoma; and effects on a fetus in situ during maternal estrogen administration. In general, lowering doses of estrogen should help eradicate or alleviate most of these effects.
Prenatal hormone administration and postnatal socialization, 1978
An interdisciplinary integrative approach must be utilized in the study of psychosexual differentiation. The approach must capitalize on data derived from non-human models, from experiments of nature, and from experiments of nurture. Studies from non-human primates strongly suggest the influence of prenatal sex hormone levels on postnatal sexually dimorphic behaviours.
Starting from this basis we have studied sixty young adult men whose mothers received, during pregnancy, diethylstilboestrol, diethylstilboestrol and natural progesterone, natural progesterone, or synthetic progesterone. They have been compared with matched controls not exposed in utero to exogenous hormones.
Studies of socialization patterns must document the differential developmental experiences, if any, of children with atypical and typical sex-typed behaviours. To this end, we are studying 60 boys whose behaviour before puberty was decidedly feminine, and their parents, and contrasting them with masculine boys and their parents. We are also studying 50 girls whose behaviour before puberty was ‘masculine’, and contrasting them with ‘feminine’ girls. Additionally, we are studying the sexually dimorphic behaviour of children of sexually atypical parents. The parents have either undergone sex-change surgery (male-to-female or female-to-male) or are homosexual.
Data from the three studies are presented. A call is made to researchers working with non-human primates to test and extend these findings.
Sex-dimorphic behaviour development in the human: prenatal hormone administration and postnatal socialization, Ciba Foundation symposium, NCBI PubMed PMID: 256835, 1978.
Signs of sexual precocity in seven children due to diethylstilbestrol exposure, 1963
“Seven boys and girls, one to nine years of age, accidentally received some diethylstilbestrol with their prescribed isonicotinic acid hydrazide (INH) owing to an error in drug manufacture. The fact that these children were on a hospital ward permitted us to make careful observation of the resultant signs and symptoms and relate them to the dose of diethylstilbestrol ingested. We wish to report these observations in detail and to call attention to the problem of drug contamination..”
Drug contamination with diethylstilbestrol. Outbreak of precocious puberty due to contaminated isonicotinic acid hydrazide (INH), New England Journal of Medicine, doi/full/10.1056/NEJM196302212680804, 1963.
Breast enlargement in two young girls following stilbestrol exposure, 1953
“The purpose of this paper is to report 2 cases of precocious secondary sexual development resulting from the ingestion of estrogenic substances by young girls, to point out the clinical peculiarities of this type of sexual precocity and to emphasize the importance of including estrogen ingestion in the differential diagnosis of pseudopuberty in females.”
Gynecomastia with pigmentation in a 10 months old male following stilbestrol exposure, 1952
“A boy, aged 10 months, showed a progressive gynaecomastia, increasing pigmentation of areolae mammae, penis and scrotum, and growth of sexual hair. The symptoms were caused by percutaneous absorption of stilbestrol. The identical picture was demonstrated experimentally in another case. — The mechanism of development of the syndrome is briefly discussed.”
“Gynecomastia with pigmentation of the nipples and areolae is reported in a four year old male following exposure to stilbestrol, which was packaged by his mother in a pharmaceutical laboratory and later in the home. This is believed to be the first case to be described.”
Gynecomastia with pigmentation in a four year old male following stilbestrol exposure, American Academy of Pediatrics, VOLUME 9 / ISSUE 1, 1952.