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Effects of tobacco smoke exposure on hormones and fertility

Institution: Sequoia Foundation
Investigator(s): Gayle Windham, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0119 Award: $115,335
Subject Area: Epidemiology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Cigarette smoke is known to contain a large number of compounds, some of which are suspected to cause damage to the reproductive system. Smoking is one of the most preventable causes of low birth weight in exposed babies and has also been associated with pregnancy loss, infant death and infertility. Some evidence also suggests that smoking may affect hormone levels, which in turn could affect pregnancy and other hormone-dependent conditions. For example, women who smoke tend to reach menopause earlier than non-smokers. We previously conducted a study that looked at different aspects of the menstrual cycle. Women kept track of their periods and collected urine daily during several cycles. From the urine , the levels of two hormones which are secreted from the ovaries during each "normal" menstrual cycle, namely estrogen and progesterone, were measured. We found that menstrual cycles of heavy smokers tended to be shorter and more irregular than those of non-smokers. There also appeared to be some differences in hormone patterns by smoking status. Shorter cycles (in general) have been linked to earlier menopause and to higher risk of breast cancer. The timing of events in the menstrual cycle, including release of progesterone and estrogen, may affect the ability to get and stay pregnant, so these findings are important for reproductive fitness. This is one of the first studies to look at smoking and menstrual function in this way and the exact means by which smoke exposure may cause these changes is not clear. Therefore, we plan to pursue these findings further in this valuable database.

The release of hormones by the ovary is under the control of messages from other organs, such as the pituitary and the brain. To learn more about how smoke exposure may act on this system, we will measure one of the pituitary hormones, called follicle stimulating hormone (FSH). FSH is important in preparing for ovulation (release of the egg in the middle of the cycle) and thus may be a marker of ovarian function. Two prior studies found some increase in FSH among smokers, but FSH was measured on only a few days. We will measure FSH on each day of a sample of menstrual cycles, so we can examine patterns throughout the cycle. FSH production will be compared by smoking status and to other menstrual cycle characteristics to determine whether it is involved in the changes in menstrual function we noted among smokers in this study.

This study is directly relevant to the goals of the TRDRP to understand the biomedical effects of smoking. It is cost-effective because it uses information from a database of over 400 women and 2,000 menstrual cycles which was already collected at considerable cost and time. From this study, we expect to learn more about how smoking affects hormone systems and reproductive function. These hormone system, in turn, are critical for many other aspects of women's health.

Final Report
Cigarette smoke is known to contain a large number of compounds, some of which are suspected to cause damage to the reproductive system. Evidence also suggests that smoking may alter hormone levels, which in turn could affect pregnancy and other hormone-dependent conditions. We previously conducted a study in which 403 women kept track of their menstrual periods and collected urine daily during several menstrual cycles (over 1500 total). From the urine, the levels of two hormones that are normally secreted from the ovaries during each menstrual cycle, namely estrogen and progesterone, were measured. We found that menstrual cycles of heavy smokers tended to be shorter and more irregular than those of non-smokers. There also appeared to be some differences in hormone patterns by smoking status. The release of hormones by the ovary is under the control of messages from other organs such as the pituitary and the brain. The purpose of this study was to learn more about how smoke exposure may act on this system by measuring one of the pituitary hormones called follicle stimulating hormone (FSH). FSH is important in follicle maturation in preparation for ovulation (release of the egg in the middle of the cycle) and thus may be a marker of ovarian function. We measured daily urinary FSH levels in a sub-set of about 300 menstrual cycles, with the time of transition between two cycles being of primary interest. The aims of the project were to determine 1) if the level and pattern of follicle stimulating hormone secretion varies by smoking status and 2) if FSH secretion is related to the menstrual cycle changes we found previously.

The sub-set was selected for FSH analysis based on smoking status (most smokers and 2 cycles each of a random sample of non-smokers). This group was similar to the overall study group by menstrual cycle characteristics and most demographic characteristics. We also confirmed the finding of shorter cycles among smokers in the sub-set selected. In addition, we have examined predictors of ovarian hormone patterns in the entire study group in order to identify factors that should be considered in the data analysis. We found lower levels of urinary estrogen in women who had ever been pregnant and higher levels among Hispanics. Progesterone metabolite levels varied by the age menstruation began, reproductive history and body size. Women who smoked more tended to have higher levels of these hormones near the beginning of the cycle, which may indicate effects on adrenal function, and also lower levels of progesterone during the second half of the cycle, after ovulation

In addressing the major aims, we found that mean urinary FSH levels around the beginning of the cycle were elevated with moderate smoking (10 or more cigarettes/day), even after adjustment for other factors. FSH levels were also higher in shorter cycles. These patterns are consistent with our previous observation of shorter cycles in smokers, suggesting a shortening of the time for follicle development before ovulation by smoking. This is also consistent with some of the ovarian hormone patterns we noted in smokers. This new work will help shed light on some of the health effects noted with smoking. Changes in hormone function from smoke exposure could impact not only a woman’s ability to have children, but other significant aspects of her health as well, such as menopause and development of hormone-dependent cancers. Few studies of FSH and smoking have been conducted so these results should be pursued in other studies as well as examining other reproductive hormones by smoking.
Publications

Tobacco smoke exposure and urinary hormone excretion
Periodical: American Journal of Epidemiology Index Medicus:
Authors: Windham GC, Mitchell PR, Fenster L, Lasley BL, Waller K, Swan SH ABS
Yr: 2001 Vol: 153 Nbr: Abs: S136 Pg: