Browsing by Subject "Sex hormones"

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    Allopregnanolone during short-term smoking abstinence: associations with depressive symptoms, smoking-related symptomatology and nicotine response
    (2012-11) Allen, Alicia Marie
    Background: Allopregnanolone (ALLO) is a neuroactive steroid metabolized from progesterone and, therefore, varies by menstrual phase in premenopausal women. Previously published literature has shown that risk for relapse to smoking varies by menstrual phase. Further, recent preclinical research indicates that ALLO may protect against drug abuse behaviors. Therefore, this dissertation project aims to characterize ALLO by menstrual phase in women with and without depressive symptoms (Paper #1) and explore the effect of ALLO on smoking-related symptomatology (SRS; Paper #2) and nicotine response (NR; Paper #3) during short-term smoking abstinence. Methods: At screening, participants (n=87) were stratified by depressive symptoms status and, using a controlled cross-over study design, were randomized to testing order (i.e., follicular (F) menstrual phase followed by the luteal (L) phase or vice versa (L-F)). The six-day testing week consisted of two days of ad libitum smoking followed by four days of biochemically verified smoking abstinence. ALLO was measured twice during each testing week: during ad libitum smoking and on the fourth day of smoking abstinence. Participants completed daily forms to assess SRS during the testing week. On the fourth day of smoking abstinence, participants participated in a NR lab session. Growth curve and covariance pattern models, adjusted for menstrual phase and testing order, were used to assess the effect of ALLO on SRS and NR, respectively. Results: In the first paper (n=84), a significant menstrual phase difference was observed in the change in ALLO level during smoking cessation. Specifically, ALLO decreased by 10% in the F phase and increased by 31% in the L phase (p<0.01). There were no significant differences in ALLO levels between the depressive symptoms groups. In the second paper (n=64), the absolute level of ALLO on the day before quit was significantly associated with the following: (1) perceived stress on the day before quit (β=-2.25, p<0.01), (2) the change in perceived stress during smoking abstinence (β=0.79, p<0.01), and (3) premenstrual symptoms of pain and water retention on the day before quit (β=1.09, p<0.01; β=1.08, p<0.01; respectively). The change in ALLO during smoking abstinence was significantly associated with the following: (1) positive and negative affect on the day before quit (β=1.15, p<0.01; β=1.04, p=0.04; respectively), (2) perceived stress on the day before quit (β=-1.77, p=0.01), (3) the change in perceived stress during smoking cessation (β=0.17, p<0.01), and (4) the change in depressive symptoms on the day of quit (β=-1.52, p=0.02). Finally, in the third paper (n=77), ALLO had a significant, positive association with the following variables prior to initiation of nicotine nasal spray: systolic blood pressure (β=0.85, p=0.04), diastolic blood pressure (β=1.19, p<0.01), and subjective levels of physical symptoms (β=0.58, p<0.01), dizziness (β =0.88, p<0.01), jitteriness (β=0.90, p=0.04) and pleasantness (β=2.05, p=0.041). ALLO also had significant associations with changes in cognition from baseline to post nicotine nasal spray use: specifically, discriminability (a measure of attention; β=1.15, p=0.05), and bias (a measure of impulsivity; β=0.12, p=0.02). Conclusion: ALLO varied significantly by menstrual phase and smoking status, and had a significant effect on several measures of SRS and NR. While several of these associations were favorable (i.e., perceived stress on the day before quit and pleasantness on the fourth day of smoking abstinence), some were not (i.e., premenstrual symptoms on the day before quit and increased subjective report of physical symptoms on the fourth day of smoking abstinence). Therefore, it remains unknown whether or not ALLO is a protective factor against drug abuse behaviors. Additional research is needed to explore the role of ALLO directly on smoking cessation outcomes.
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    Effects of Green Tea Extract on Biomarkers of Breast Cancer Risk Including Reproductive Hormones and IGF axis Proteins
    (2015-08) Samavat, Hamed
    Objective: To investigate the effects of daily intake of a highly concentrated green tea extract (GTE) for one year on circulating sex hormones and insulin-like growth factor (IGF) proteins as well as urinary estrogens and estrogen metabolites in postmenopausal women with different catechol-O-methyltransferase (COMT) genotypes. Method: The Minnesota Green Tea Trial (MGTT) is a randomized, double-blind, placebo-controlled, phase II clinical trial. Healthy postmenopausal women with heterogeneously or extremely dense breast tissue (age = 59.78 ± 5.02 years; body mass index= 25.70 ± 8.21 kg/m2) were randomly assigned to the GTE group (n=538) and were given 4 capsules a day, each containing 200 mg epigallocatechin gallate (EGCG) and the others (n=537) to the placebo group. Participants were 93% non-Hispanic white and non-current hormone users. Twenty-four hour urine samples were collected at month 0 and at the end of the study, and fasting blood samples were drawn at months 0, 6 and 12. Circulating and urinary estrogens, as well as urinary estrogen metabolites were quantified by the liquid chromatography-tandem mass spectrometry method. Blood IGF axis proteins were analyzed by ELISA. Results: GTE supplementation was associated with reduced urinary estriol levels (P= 0.02) and higher urinary 2-hydroxyestrone (P= 0.02) compared to the placebo. There was also less of a reduction in the urinary levels of 16α-hydroxyestrone in the GTE versus placebo group. Intake of the GTE resulted in significant increase of circulating estradiol and testosterone and their corresponding free and bioavailable fractions, whereas these measures were reduced in the placebo group. Additionally, COMT genotype did not modify the GTE effect on either circulating sex hormones and IGF proteins or urinary estrogens. Conclusion: Daily intake of high-dose of green tea extract for 12 month exerts modest effects on urinary excretion of estrogen metabolites, yet these effects are not modified by the COMT polymorphisms. Potential breast cancer protective effects of GTE are not mediated by alterations in circulating sex hormones or IGF axis proteins.