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To the Editor: Neisseria gonorrhoeae is a common etiologic agent of pelvic inflammatory disease (PID).¹ The development of PID is likely determined by both host susceptibility and the virulence of the organism, and there is clinical evidence that changes in host susceptibility are influenced by hormonal status. For instance, the incidence of gonococcal PID symptoms is highest during the early proliferative phase of the menstrual cycle, and PID is less prevalent among women who use oral contraceptives.^1-4 Furthermore, men rarely develop ascending gonococcal infections. Since complement activity is an important defense against PID,⁵ we wanted to determine if complement activity is cyclic and thus correlated with resistance to gonococcal infection.

Method
To investigate possible cyclic changes in serum properties, we evaluated the antibacterial activity of multiple serum samples obtained from 4 female volunteers, aged 25 to 35 years, at different phases of the menstrual cycle. All women had regular 28-day cycles, had no history of sexually transmitted disease, and were not receiving oral contraceptives. A pooled serum sample from 10 male volunteers (purchased from Sigma, St Louis, Mo) was also evaluated. Each serum sample was evaluated for the elimination of N gonorrhoeae strain 2005. The functional state of the complement system of each serum sample was assessed by the standard method of measuring total complement hemolytic activity (CH₅₀).⁶

Results
The antigonococcal effect of the serum was weakest at the early proliferative phase for all 4 women (Figure 1). The highest antigonococcal activity of serum was observed during the midcycle. Interestingly, CH₅₀ was lowest in the early proliferative phase and highest at midcycle, paralleling the changes in antigonococcal activity. Male serum samples showed 55% bactericidal activity and had an average CH₅₀ level of 125 U/mL.

View larger version (19K): [in this window] [in a new window] Figure. Gonococcal Elimination Property and Complement Hemolytic Activity of Human Serum During the Menstrual Cycle CH50 indicates total complement hemolytic activity. Subjects were healthy women aged 25 to 35 years with regular 28-day menstrual cycles and without history of sexually transmitted disease. Each data point represents the average serum results from 4 subjects, each of whom provided serum at days 1, 7, 14, 21, and 28 of 3 separate menstrual cycles. Each sample was tested 3 times. Error bars represent SEM. The t test showed a statistically significant difference (P<.005) between day 1 and day 14.

Comment
We have demonstrated that both complement function and antibacterial activity of serum change cyclically in women, suggesting that sex hormones are involved in systemic immune function. It is possible that the physiologic decrease in complement function during menstruation may be a window of opportunity for N gonorrhoeae to colonize, invade, and cause ascending infection. These cyclic changes in host defense may be important not only in PID, but also in the pathogenesis of other infectious diseases in women. Further understanding of the link between the menstrual cycle and changes in host defense may generate novel strategies to prevent PID.

Stella Nowicki, DDS; Audrey Hart-Van Tassell, BA; Bogdan Nowicki, MD, PhD
University of Texas Medical Branch at Galveston

1. McCormack WM. Pelvic inflammatory disease. N Engl J Med. 1994;330:115-119. FREE FULL TEXT 2. Sweet RL, Blankfort-Doyle M, Robbie MO, Schachter J. The occurrence of chlamydial and gonococcal salpingitis during the menstrual cycle. JAMA. 1986;255:2062-2064. ABSTRACT 3. Wolner-Hansen P, Eschenbach DA, Paavonen J. Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use. JAMA. 1990;263:54-59. ABSTRACT 4. McCormack WM, Reynolds GH. Effect of menstrual cycle and method of contraception on recovery of Neisseria gonorrhoeae. JAMA. 1982;247:1292-1294. ABSTRACT 5. Nowicki S, Ram P, Pham T, et al. Pelvic inflammatory disease isolates of N gonorrhoeae are distinguished by C1q-dependent virulence for newborn rats and by sac-4 region. Infect Immun. 1997;65:2094-2099. ABSTRACT 6. Frank MM. Detection of complement in relation to disease. J Allergy Clin Immunol. 1992;89:641-648. PUBMED

Letters Section Editors: Phil B. Fontanarosa, MD, Deputy Editor; Stephen J. Lurie, MD, PhD, Fishbein Fellow.

JAMA. 2000;283:1291-1292.

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