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- Hallberg, Gunilla
(författare)
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Effects of Endogenous and Exogenous Hormones on the Female Breast : With Special Reference to the Expression of Proteoglycans
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation. In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03). We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found. In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).
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| 2. |
- Akhter, Tansim, 1967-
(författare)
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Carotid Artery Wall Layer Dimensions during and after Pre-eclampsia : An investigation using non-invasive high-frequency ultrasound
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated.Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older.Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system.Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk.Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects.Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.
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