A study of infertility treatment and melanoma

Abstract

This study examined the possible association between melanoma and exposure to fertility drugs, specifically clomiphene citrate, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A cohort of 3186 women who attended a fertility clinic between 1 January 1980 and 31 December 1990 was studied; by January 1996, 14 women had been diagnosed with primary melanoma. Details of fertility treatment were extracted from the clinical records. The incidence of melanoma in the cohort resembled that of the female Queensland population (standardized incidence ratio = 0.89, 95% confidence interval [CI] = 0.54-1.48). Exposure to clomiphene citrate, HMG or HCG did not affect the incidence of melanoma. Women with infertile partners who were treated with fertility drugs were at increased risk of melanoma (odds ratio [OR] = 3.17, 95% CI = 1.01-9.98). Compared with women exposed only to clomiphene citrate and HMG, a lower incidence of melanoma was observed among those who received HCG as well (OR = 0.10, 95% CI = 0.02-0.42). Women exposed to two or more cycles of either clomiphene citrate (OR = 0.27, 95% CI = 0.08-0.94) or HMG (OR = 0.23, 95% CI = 0.07-0.84) had a significant reduction in melanoma risk compared with women exposed to no or one cycle. In summary, a woman's infertility per se was not found to be associated with melanoma, while exposure to fertility drugs was positively associated with melanoma in women with infertile partners and negatively associated in women with low doses of fertility drugs.

Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

“…In line with our results, Althuis et al [26] observed no increased risk after use of gonadotrophins and Rossing et al [24] found no increased risk after clomiphene use. However, Althuis et al [26] found an increased risk in women who used clomiphene and remained nulliparous through follow-up and Young et al [27] found a lower risk in clomiphene-users. The analyses by Young et al [27], however, were based on only 14 exposed cases of which six cases were in situ melanoma.…”

“…Two case-control studies found no significantly increased risk, but were unable to distinguish among different types of fertility drugs [7,25]. Only three cohort studies [24,26,27] have estimated malignant melanoma risk after use of specific types of fertility drugs (clomiphene, gonadotrophins, hMG and hCG) using within cohort analyses. Hence, we can only compare our results to those studies due to the anticipated different effects of different types of fertility drugs.…”

“…A total of 133 women were diagnosed with malignant melanoma (International Classification of Diseases for Oncology, 7th Revision (ICD-7)) during the follow-up period. For comparison, a subcohort of 1,360 women were randomly selected from the cohort in four strata of age at cohort entry (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), 31-36 and 37-55 years) and in five strata of calendar year of cohort entry (1963-1977, 1978-1984, 1985-1989, 1990-1996, and 1997-1998), equaling 20 strata.…”

“…Two case reports have indicated that use of clomiphene may increase risk of developing malignant melanoma [18,19]. However, the few epidemiologic studies which have investigated the possible association have been equivocal as most studies found no association [7,[20][21][22][23][24][25], whereas one study observed an increased risk [26] and one study found a lower risk [27]. Provided the increasing number of prescriptions of fertility drugs among infertile couples over the last 30 years [15][16][17], and the generally increasing incidence of malignant melanoma in women of most Western countries [28], the question of whether fertility drugs may increase malignant melanoma risk is of great public health concern.…”

Ovarielle Stimulation und Karzinomrisiko

“…Lediglich bei Frauen mit infertilen Partnern, die mit humanem menopausalen Gonadotropin (HMG) und mit Clomiphen behandelt wurden, trat ein erhöhtes Risiko für ein malignes Melanom auf (OR 3,17, 95%-KI 1,01-9,98). In dieser Arbeit wurde auch der Einfluss der Anzahl Therapiezyklen auf das Melanomrisiko untersucht: So haben Patientinnen mit zwei oder mehr Zyklen HMG (OR 0,23, 95%-KI=0,07-0,84) oder Chlomiphen (OR 0,27, 95%-KI 0,08-0,94) im Vergleich zu Patientinnen mit nur einem oder keinem Zyklus eine signifikant niedrigere Inzidenz für ein malignes Melanom [16]. Diese Daten zeigen eine positive Assoziation zwischen dem Einsatz von Ovulationsinduktoren und malignen Melanomen bei Frauen von infertilen Partnern und eine negative Assoziation bezüglich der niedrigen Dosierung der Substanzen.…”