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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

Hietala, M; Törngren, Therese LU ; Borg, Åke LU ; Olsson, Håkan LU and Jernström, Helena LU (2007) In Human Reproduction 22(1). p.83-91
Abstract
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... (More)
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 (P-trend =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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, oral contraceptives, androgen receptor polymorphism, premenopausal women, testosterone levels
in
Human Reproduction
volume
22
issue
1
pages
83 - 91
publisher
Oxford University Press
external identifiers
  • wos:000243065300010
  • scopus:33845657461
ISSN
0268-1161
DOI
10.1093/humrep/del318
language
English
LU publication?
yes
id
425320fa-6091-4924-a1a6-93453fe9e91b (old id 681701)
date added to LUP
2007-12-12 13:52:24
date last changed
2017-01-01 04:51:33
@article{425320fa-6091-4924-a1a6-93453fe9e91b,
  abstract     = {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 &lt;= 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 &lt;= 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 (&gt;= 17 repeats) was significantly associated with lower testosterone levels in OC users during cycle days 5-10 (P-trend =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.},
  author       = {Hietala, M and Törngren, Therese and Borg, Åke and Olsson, Håkan and Jernström, Helena},
  issn         = {0268-1161},
  keyword      = {breast cancer,oral contraceptives,androgen receptor polymorphism,premenopausal women,testosterone levels},
  language     = {eng},
  number       = {1},
  pages        = {83--91},
  publisher    = {Oxford University Press},
  series       = {Human Reproduction},
  title        = {Testosterone levels in relation to oral contraceptive use and the androgen receptor CAG and GGC length polymorphisms in healthy young women},
  url          = {http://dx.doi.org/10.1093/humrep/del318},
  volume       = {22},
  year         = {2007},
}