Hum. Reprod. Advance Access originally published online on August 18, 2006
Human Reproduction 2007 22(1):83-91; doi:10.1093/humrep/del318
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Testosterone levels in relation to oral contraceptive use and the androgen receptor CAG and GGC length polymorphisms in healthy young women
1 Department of Oncology and 2 Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden
3 To whom correspondence should be addressed at: Helena Jernström, Department of Oncology, Clinical Sciences, Lund University, Barngatan 2:1, SE-221 85 Lund, Sweden. E-mail: helena.jernstrom{at}med.lu.se
BACKGROUND: The combined effect from the androgen receptor (AR) CAG and GGC length polymorphisms on testosterone levels has not been studied in young women. METHODS: Testosterone levels were measured in blood drawn on both menstrual cycle days 5–10 and 18–23 in 258 healthy women, aged 
40 years, from high-risk breast cancer families. CAG and GGC length polymorphisms were analysed by PCR and fragment analyses. All women completed a questionnaire including information on oral contraceptive (OC) use and reproductive factors. RESULTS: OC users had lower median testosterone levels than non-users during cycle days 5–10 and 18–23 (P 0.005 for both). The BRCA mutation status was associated neither with testosterone levels nor with CAG or GGC length polymorphism. The CAG length polymorphism was not associated with testosterone levels. The cumulative number of long GGC alleles (
17 repeats) was significantly associated with lower testosterone levels in OC users during cycle days 5–10 (Ptrend =0.014), but not during cycle days 18–23 or in non-users. The interaction between the GGC length polymorphism and OC status was highly significant during cycle days 5–10 (P = 0.002) and near-significant during days 18–23 (P = 0.07). Incident breast cancer was more common in women with two short GGC alleles (log-rank P = 0.003). CONCLUSION: The GGC repeat length was the only significant genetic factor modifying the testosterone levels in current OC users from high-risk families. Homozygosity for the short GGC allele may be linked to the increased risk of early-onset breast cancer after OC exposure in high-risk women.
Key words: androgen receptor polymorphism/breast cancer/oral contraceptives/premenopausal women/testosterone levels