Circulating prolactin concentrations and risk of type 2 diabetes in US women

Aims/hypothesis

Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain.

Methods

We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses’ Health Study (NHS) and NHSII with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989–1990; NHSII 1996–1999) and a subset of 998 NHS women providing a second blood sample during 2000–2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression.

Results

A total of 699 incident type 2 diabetes cases were documented during 156,140 person-years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; p_trend?=?0.02). The associations were similar by menopausal status and other risk factors (p_interaction?>?0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, p_difference?=?0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9 years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw.

Conclusions/interpretation

A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9–10 years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.

     

A prospective study of leisure‐time physical activity and risk of incident epithelial ovarian cancer: Impact by menopausal status

Despite multiple hypotheses for a protective effect, epidemiologic findings are inconsistent regarding the association between physical activity and risk of ovarian cancer. Considering physical activity assessment at different times of life, including pre‐ and postmenopause, may be important for explaining these discrepancies. Therefore, we examined the risk of ovarian cancer according to total, premenopausal and postmenopausal physical activity among 85,462 women from the Nurses' Health Study and 112,679 women from the Nurses' Health Study II. Leisure‐time physical activity was prospectively assessed about every 2–4 years using validated questionnaires, and characterized as metabolic equivalent task hours per week (MET‐hr/week), which combines exercise duration and intensity. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for these associations. We identified 815 incident epithelial ovarian cancer cases during 24 years of follow‐up. A modestly increased ovarian cancer risk was observed for high levels of total cumulative average physical activity and a suggestively increased risk for low activity. Compared to 3–9 MET‐hr/week, HRs (95% CIs) were 1.26 (1.02, 1.55) for ≥27 MET‐hr/week (equivalent to 1 hr/day of brisk walking) and 1.19 (0.94, 1.52) for <3 MET‐hr/week. This association was limited to premenopausal physical activity [comparable HR (95% CI) of 1.50 (1.13, 1.97) and 1.29 (0.95, 1.75), respectively]. Postmenopausal physical activity was not associated with risk. Our data do not support a protective role of physical activity for ovarian cancer. The increased risk associated with physical activity during premenopausal years and the underlying etiology require further investigation.     

Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women

Purpose

Common analgesics (aspirin, non-aspirin NSAIDs, and acetaminophen) may be associated with hormone-related cancers, possibly via effects on sex hormone and prolactin concentrations.

Methods

Between 1996 and 1999, 29,611 participants in the Nurses’ Health Study II (NHSII) provided blood samples; 18,521 provided samples timed in the early follicular and mid-luteal phases of the menstrual cycle, the remainder provided untimed samples. We assessed the cross-sectional relationship between analgesic use and plasma sex hormone and prolactin concentrations among 2,034 premenopausal women, 32–54 years old, who served as controls in nested case–control studies, or participated in a within-person hormone reproducibility study in the NHSII; this included 1,700 timed and 334 untimed samples. Estrogens and progesterone were measured in timed samples; androgens and prolactin were measured in timed and untimed samples.

Results

In multivariable models, non-aspirin NSAIDs were positively associated with follicular free estradiol [13.5 % higher, use ≥4 days/week vs. nonusers (p = 0.04; p _trend = 0.11)]; results for follicular total estradiol were similar (13.2 % higher, p = 0.06; p _trend = 0.11). Acetaminophen use was inversely associated with prolactin (11.8 % lower, use 2 days/week vs. nonusers, p = 0.01, p _trend = 0.04). Acetaminophen was also inversely associated with free testosterone (7.1 % lower, use 2 days/week vs. nonusers, p = 0.04; p _trend = 0.04). No other associations were observed with the other hormones, or with aspirin use.

Conclusions

There were no clear patterns between analgesic use and sex hormones in premenopausal women. Acetaminophen use may be modestly associated with prolactin and free testosterone. Our results do not support that analgesic use influences cancer risk through alterations in premenopausal circulating sex hormones or prolactin.     

Associations of established breast cancer risk factors with urinary estrogens in postmenopausal women

Cancer Causes & Control - Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and...     

The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study

Introduction  

Sex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.     

Menstrual pain and epithelial ovarian cancer risk

Purpose

Menstrual pain is associated with increased production of inflammatory molecules, such as prostaglandins. Inflammation is involved in pathogenesis of several cancers, including ovarian cancer. In this study, we examined the association between menstrual pain and risk of ovarian cancer.

Methods

We conducted a case–control study with 2,028 cases of epithelial ovarian cancer and 2,091 age- and study center-matched controls. Women were asked to report the severity of menstrual pain during their twenties and thirties, when not using oral contraceptives or breastfeeding. We used an unconditional logistic regression to evaluate the association between menstrual pain and epithelial ovarian cancer risk overall, and polytomous logistic regression to evaluate whether the association differed across tumor subtypes.

Results

Risk of ovarian cancer was increased in women with moderate (OR 1.22, 95 % CI 1.05–1.42) and severe pain (OR 1.34, 95 % CI 1.09–1.65) compared to women with no or mild pain during menstrual period. The association differed by histologic subtypes, with significant associations for severe pain with endometrioid (OR 1.64, 95 % CI 1.15–2.34) and clear cell tumors (OR 1.91, 95 % CI 1.11–3.28).

Conclusions

Our data suggest that moderate and severe pain during menstrual period are associated with increased risk of epithelial ovarian cancer. Due to high prevalence of menstrual pain in women of reproductive age, this observation warrants further studies.     

Effects of a moderate intensity exercise intervention on estrogen metabolism in postmenopausal women.

Physical activity has been associated with reduced breast cancer risk, potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) also has been associated with reduced breast cancer risk. Studies suggest that body composition and exercise can influence estrogen metabolism. We determined the effects of a 12-month moderate intensity aerobic exercise intervention on urinary 2-OH E(1), 16alpha-OH E(1), and their ratio in overweight and obese, previously sedentary, postmenopausal women, ages 50-75 years. Women were randomized to a 12-month exercise intervention (n = 87) or stretching control group (n = 86); 170 completed the study. Urinary 2- and 16alpha-OH E(1) were measured in spot urines collected at baseline, 3, and 12 months. Body composition was measured at baseline and 12 months. Differences between exercisers and controls for excretion of estrogen metabolites were determined using general estimating equations. Further analyses assessed change in estrogen metabolites and their ratio by subgroups of change in body composition. Overall, there were no significant effects of the exercise intervention on 2-OH E(1), 16alpha-OH E(1), or their ratio (P > 0.05). There appeared to be an effect of change in intra-abdominal fat and adherence to the exercise intervention on change in the estrogen metabolites or their ratio. However, this did not reflect a potentially desirable change in estrogen metabolites associated with the exercise intervention. Thus, this 12-month moderate intensity exercise intervention did not significantly alter urinary excretion of 2-OH E(1), 16alpha-OH E(1), or their ratio in this population of women.