International Agency for Research on Cancer (IARC)
Summaries & Evaluations
CLOMIPHENE CITRATE
(Group 3)
For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 172)
Clomiphene
CAS No.: 58-22-0
Chem. Abstr. Name: 2-[4-(2-Chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine
Clomiphene citrate
CAS No.: 50-41-9
Chem. Abstr. Name: 2-[4-(2-Chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine-
2-hydroxy-1,2,3-propanetricarboxylate (1:1)
A. Evidence for carcinogenicity to humans (inadequate)
Only case reports of benign and malignant tumours occurring at various sites are available [ref: 1-5]. These include testicular tumours in three young men who had received clomiphene as part of hormonal treatment for oligospermia [ref: 2], a hepatoblastoma in a female infant whose mother had received clomiphene citrate as treatment for infertility [ref: 3], a liver-cell adenoma in a woman who had received clomiphene citrate for oligomenorrhoea [ref: 4], and unilateral testicular neoplasms in two of 650 oligospermic men who had received monthly treatments with clomiphene citrate (daily for three weeks followed by a week of rest) for six to 12 months [ref: 5].
B. Evidence for carcinogenicity to animals (inadequate)
Clomiphene citrate was tested in an inadequate experiment in newborn rats by single subcutaneous injection; reproductive-tract abnormalities, including uterine and ovarian tumours, were reported [ref: 1].
C. Other relevant data
No data were available on the genetic and related effects of clomiphene citrate in humans. It did not induce chromosomal aberrations or micronuclei in bone-marrow cells of mice treated in vivo [ref: 6].
Overall evaluation
Clomiphene citrate is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluation: Vol. 21 (1979)
References
1. IARC Monographs, 21, 551-561
2. Neoptolemos, J.P., Locke, T.J. & Fossard, D.P. (1981) Testicular tumour associated with hormonal treatment for oligospermia. Lancet, ii, 754
3. Melamed, I., Bujanover, Y., Hammer, J. & Spirer, Z. (1982) Hepatoblastoma in an infant born to a mother after hormonal treatment for steriligy. New Engl. J. Med., 307, 820
4. Carrasco, D., Barrachina, M., Prieto, M. & Berenguer, J. (1983) Clomiphene citrate and liver cell adenoma. New Engl. J. Med., 310, 1120-1121
5. Nilsson, A. & Nilsson, S. (1985) Testicular germ cell tumors after clomiphene therapy for subfertility. J. Urol., 134, 560-562
6. IARC Monographs, Suppl. 6, 184-185, 1987
Synonyms for Clomiphene
* Chloramiphene
* 2-para-(2-Chloro-1,2-diphenylvinyl)-phenoxy]triethylamine
* 2-para-(b-Chloro-a-phenylstyryl)phenoxy]triethylamine
* Clomifene
* Clomiphene B
Synonyms for Clomiphene citrate
* Clomiphene dihydrogen citrate
* 2-[p-(2-Chloro-1,2-diphenylvinyl)phenoxy]triethylamine citrate (1:1)
* Clomid
* Clomifeno
* Clomivid
* Clomphid
* Chloramiphene
* Dyneric
* Genozym
* Ikaclomin
* Mer-41
* MRL 41
* MRL/41
* NSC 35770
* Omifin
* Racemic clomiphene citrate
Last updated: 9 March 1998
International Agency for Research on Cancer (IARC)
Summaries & Evaluations
CLOMIPHENE AND CLOMIPHENE CITRATE
VOL.: 21 (1979) (p. 551)
5. Summary of Data Reported and Evaluation
(N.B. - This section should be read in conjunction with the General Remarks on Sex Hormones and with the General Conclusions on Sex Hormones.)
5.1 Experimental data
Clomiphene citrate was inadequately tested in one experiment in newborn rats by subcutaneous injection; uterine and ovarian tumours were reported.
Clomiphene citrate is embryolethal for pre- and postimplantation embryos in several species and has various teratogenic effects in rats.
5.2 Human data
There are a few case reports of the occurrence of malignant and benign tumours at various sites in patients treated with clomiphene citrate, but there is no evidence of a causal relationship.
No definite association between clomiphene citrate administration and congenital defects in humans has been demonstrated.
5.3 Evaluation
The available experimental and human data are insufficient to evaluate the carcinogenicity of clomiphene citrate.
Subsequent evaluation: Suppl. 7 (1987)
Last updated 01/12/98
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