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STOCKHOLM, Oct. 31 - Women with recurrent yeast infections appear to have lower-than-normal morning levels of salivary cortisol, a sign of stress that could indicate an increased vulnerability to candida, according to a pilot study.

On the other hand, the Karolinska Institute investigators conceded, it could be that recurrent yeast infections produce chronic stress.

The investigators found that among 35 women with recurrent vulvovaginal candida, morning cortisol levels from saliva samples were significantly lower (P<.002) during the first 45 minutes after waking up, compared with 35 women who did not have frequent yeast infections.

These women may be more vulnerable to recurrent candida vulvovaginosis and other infections because chronic stress impairs immunity, explained a research team led by Sophia M. Ehrström, M.D., and colleagues reported in the October issue of American Journal of Obstetrics and Gynecology.

Although cortisol typically rises in the morning, paradoxically, a lethargic cortisol level at that time of day could indicate chronic stress, the authors said.

The recurrent yeast infection group reported more genital infections overall. For example, the study also found 53% percent of the recurrent yeast infection group reported a history of bacterial vaginosis infection versus 9% among the controls, (95% confidence interval, 2.7-72.5, P<.001) and 43% reported a history of condyloma versus 6% in the control group (95% CI 2,3-122, P<.001).

However, they wrote, infection "is a condition per se that may produce chronic stress." The annoying symptoms of yeast infection, such as the repetitive itching, for example, may interfere with daily function and even sex, which could then impact relationships, they said.

The study compared two groups of women with a mean age of 27 and who had no significant differences in body mass index or median age at first sexual intercourse. The women were asked to answer a questionnaire to provide details about their lifestyle, sexual behavior, and past medical history, including whether they used oral contraceptives. All 35 patients with recurrent yeast infections had experienced a minimum of four yeast infections in the past year.

All of the women underwent an examination of the vulva and vagina. The research team collected vaginal samples for fungal cultures. The women also provided blood samples on days five and 11 of their menstrual cycles to have their hormone levels measured.

The night before the saliva samples were collected, the women were advised not to drink, eat, brush their teeth or smoke. Each participant received cotton wool swabs called Salivettes. On the day of collection, the participants chewed a Salivette for 40 seconds to boost salivary flow. They did this upon awakening and then 15 minutes after waking up, again at 30 minutes and 45 minutes. They were instructed to store the chewed swabs in the freezer until they had to bring them to the hospital. These were the samples used to measure morning cortisol levels.

In addition to lower morning cortisol levels, the yeast infection patients also reported more gastrointestinal problems, including flatulence (60% vs. 14% in the controls, P<.001) and gastritis (43% vs. 14%, respectively, P=.02). The authors said earlier studies have linked gastrointestinal symptoms with stress.

Compared with the controls, the participants with recurrent yeast infections had significantly lower cortisol levels 15 minutes after awakening (P=.01), at a half hour (P=.001) and also at 45 minutes (P=.01). Although oral contraceptive use has previously been associated with a propensity for yeast infections, the authors found birth control pills made no significant difference.

None of the study participants were in the luteal phase at the time of the blood sample collection. The researchers found no significant differences in levels of glycosylated hemoglobulin, sexual hormone-binding globulin, dihydroepiandrosterone, testosterone, cholesterol, or thyroid-stimulating hormone.

Dr. Ehrström and her team acknowledged that while their study sample was small and relied on some self-reported information, "the results of our study show that chronic stress may play a role in the pathogenesis of recurrent candid vulvovaginitis." They said more study is needed to flesh out any potential relationship between the two factors.

Yvonne S. Thornton, M.D., a professor of clinical obstetrics at Weill Cornell Medical College in New York, was not impressed.

"The data were poorly gathered and you cannot come to a conclusion that when you're stressed you're going to have an increased risk to vaginal yeast infections," Dr. Thornton said in an interview.

Too few variables were controlled, Dr. Thornton said. For example, it's unclear whether the participants were early-bird risers or late-risers, which could affect their cortisol levels, she said. Also, considering that yeast infection is so common, the study sample could have easily been much larger, which could have yielded clearer results, Dr. Thornton said.

"There are just too many confounding variables," she said. The study "has no applicability to the general population."

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