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Cigarette Smoking and Effects on Hormone Function in Premenopausal Women

Catherine McDiarmid-Watt | Saturday, December 08, 2007 | 0 comments

Cigarette smoking appears to have a prolonged, adverse effect on ovarian function. Byproducts of smoking include nicotine and cadmium, which have been demonstrated to inhibit granulosa cell aromatase activity in vitro and may have an antiestrogen effect. Polyaromatic hydrocarbons may enhance steroid hormone metabolism, while other cigarette alkaloids seem to inhibit progesterone synthesis.[1,2] Smoking seems to affect fertility through delayed conception; increasing risk for spontaneous abortion; and for those undergoing fertility treatments, reducing response to ovarian stimulation, implantation, and carrying the pregnancy to term.[2,3]

Cigarette smoking seems to cause variation in menstrual cycle function. Smokers, particularly heavy smokers, have shorter, more variable cycles and more varied lengths of menstrual periods. These findings suggest that smokers might have abnormal folliculogenesis and a short luteal phase due to inadequate progesterone production, which may contribute to infertility.[3]

The authors of this study examined the effects of smoking on excretion of urinary hormone metabolites throughout the menstrual cycle.

Methods - The study was conducted using data derived from the Women's Reproductive Health Study. In this study, 403 premenopausal women ages 18 to 39 years were evaluated prospectively on menstrual function and miscarriage. Study participants collected samples of first morning urine on a daily basis, with a mean of 3.6 complete cycles and 92% of study days. Detailed telephone interviews were conducted to ascertain demographics, reproductive history, lifestyle factors, and current and past smoking history along with other exposures. Study participants kept daily diaries in which they recorded urine collection, vaginal bleeding, intercourse, contraception, and the number of cigarettes smoked daily. Smokers were divided into 3 categories: low (1 to 9 cigarettes per day), moderate (great than 10 per day), and heavy (greater than 20 per day).

Urine was assayed for smoking metabolites, steroid metabolites, and levels of follicle-stimulating hormone (FSH). Estrone sulfate and estrone glucuronide (estrone conjugates [(E1C]) and the progesterone metabolite pregnanediol-3-glucuronide (PdG) were measured by immunoassay on a daily basis. Ovulatory status for each cycle was determined based on the increase in PdG. The day of ovulation was established using an algorithm to calculate E1C-PdG ratio in a 5-day window of increasing PdG and decreasing E1C levels. Menstrual cycles were divided into follicular phase (the first day of menses to ovulation) and luteal phase (the day after ovulation to the first day of menses) and then subdivided into short or long cycles. For graphing purposes, cycles were centered at the day of ovulation.

Urine assays for FSH were used to further define the transition from the follicular to the luteal phase based on increasing levels of FSH. Levels of FSH were measured from 7 days before menses to 17 days after. The maximum level of FSH was determined, along with the day of the cycle on which it occurred.

Results - Daily FSH levels were higher in smokers than in nonsmokers; moderate to heavy smokers had levels significantly higher than nonsmokers. Older women and nonwhites also had higher levels. The levels of FSH in smokers peaked at a higher level than those of nonsmokers in the follicular-luteal phase transition. Smokers reached the mid-cycle peak more than 1 day earlier than nonsmokers. However, there was no difference between the 2 groups with no pregnancies or those with pregnancies carried to term. Smokers had slightly higher pregnancy losses than nonsmokers (34.4% vs 29%).

Heavy smokers had higher levels of E1C and PdG at baseline (22% vs 40%, respectively), but these numbers did not reach statistical significance. The levels of PdG were lower in the luteal phase for smokers and 25% lower for heavy smokers.

Conclusion - Smoking affects levels of FSH, progesterone, and estrogen throughout the menstrual cycle.

Commentary - This study appears to add evidence to prior studies that cigarette smoking negatively affects menstrual function.[4] The levels of FSH were higher in smokers than in nonsmokers, as has been found in other studies.[5] It is theorized that reduced progesterone levels lead to higher FSH levels, a shorter follicular phase, and possibly reduced follicle development. Since progesterone is important for endometrial response, an inadequate luteal phase would increase fetal loss. This study did not find a difference between smokers and nonsmokers in terms of pregnancies and live births, but it did find that smokers had a higher number of pregnancy losses, although the numbers did not reach statistical significance.

Differences between smokers and nonsmokers might have been greater if larger numbers had been used. While the study enrolled 403 participants, data presented in this article were based on 125 of the participants. One prior study did not find smoking related to changes in hormone levels, but that study evaluated perimenopausal as opposed to premenopausal women; thus, changes in hormone levels may be more likely to be attributable to age, and smoking may have less of an effect.[6]

Overall, this study adds to evidence that smoking has deleterious effects on ovarian function, although further study is warranted.

Ful larticle: http://www.medscape.com/viewarticle/517949_2


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Catherine

About Catherine: I am mom to three grown sons, two grandchildren and two rescue dogs. After years of raising my boys as a single mom, I remarried a wonderful man who had never had a child of his own. Unexpectedly, I found myself pregnant at 49!
Sadly we lost that precious baby at 8 weeks, and decided to try again. Five more losses, turned down for donor egg, foster care and adoption due to my age and losses - we have accepted that there will be no more babies in our house.

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