Female Hormones

The following articles are reposts from the old LymeNet FLASH board. The researcher mentioned is Marylynn Barkley, MD, PhD, UC Davis Section of Neurobiology, Physiology, & Behavior.

How female hormones may affect symptoms ~ See page 31

THE LYME TIMES- Publication of the Lyme Disease Resource Center

Marylynn Barkley, MD. PhD, UC Davis Section of Neurobiology, Physiology & Behavior,is conducting a study on the relation of female hormones to the waxing and waning of Lyme disease symptoms. She has observed an intensification of night sweats (diaphoresis) in women with Lyme disease immediately before and during the menses. At the end of the menstrual cycle, there is a precipitous decline in ovarian steroid hormones which triggers the shedding of the uterine lining. During this period, recognition of Borrelia antigen by the Lyme Urine Antigen Test (LUAT) also reaches a peak, and cytokine levels are above normal.

Night sweats are thought to reflect activation of the immune system and have historically been used to monitor infections in patients with tuberculosis, malaria, and other diseases. Dr. Barkley discussed a patient whose classical Lyme disease symptoms were not recognized until 18 months after an initial flulike illness. The patient. initially seronegative, became positive after an empiric trial of antibiotic therapy. She experienced regularly occurring night sweats which were measured according to an objective scale for intensity (level 4: most intense, IOcc fluid could be wrung out of garment, to level 1: only front of garment was wet).

Data recorded over a two-year period showed intensification of night sweats (more level 4 events) in a cyclic pattern coinciding with the decline of ovarian hormones and the onset of the menses. Over time the intensity of the night sweats lessened, suggesting response to therapy. Continuing her study with another patient. Dr. Barkeley wanted to discover whether there was an objective relationship between progestin levels and Bb antigen activity. Using the LUAT, she discovered an increased recognition of Bb antigen as progesterone levels fell.

In a further study of 26 women, 21 reported night sweats, and of those who kept records, the most intense night sweats were in association with menstruation. She also discovered a significant correlation with intensification of Lyme disease symptomatology (arthralgia, myalgia, cognitive deficits, fatigue) around the same time.

Dr. Barkeley concluded that there is an interval of increased immune activity during several days before and

after the onset of menses. She is assuming that the night sweat activity is proportional to the spirochete abundance.

She speculates that the increase in immune response kills an increased number of spirochetes during this period, which leads to the intensified symptomatology and the increased shedding of antigen.

One practical application of Dr. Barkley's work is to suggest an optimal time for urine collection for LUAT in menstruating women.

Collecting during the 3 days pro and post onset of menses will maximize the chance of a positive result.

Continued on back page- page 31- the Lyme Times....

Another possibility is that the timing of a tick bite in the menstrual cycle may also affect the likelihood of infection or resistance to infection.

Dr. Barkeley made the interesting observation that there are two peak incidences of autoimmune illness in women; one is around the time of puberty, the other is at menopause. Evolutionary ecologists point out that historically, women have not experienced many recurrent menstrual cycles. The fact that many modem women now do, may impinge upon their immune systems and compromise recognition of self. Dr. Barkeley noted that many of the women randomly included in her study got their Lyme disease in their late 30s or early 40s, leading her to wonder if their immune systems had indeed been compromised. But that is subject for a further study.

In the question period. Dr. Barkcley described three young women who had tried birth control pills to see if they would alleviate some of their Lyme disease symptoms. Their symptoms intensified so much they were unable to continue or the pills.

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NUMBER 19 Education, Support, Advocacy. Research NOVEMBER-DECEMBER 1997

http://www.igenex.com/newsset1.htm

Presented at the 10th Annual International Conference on Lyme Borreliosis, NIH, Bethesda, Maryland

April 28-30, 1997

The Lyme Urine Antigen Test (LUAT) During Antibiotic Therapy in Women with Recurrent Menstrual Cycles

M. Barkley, MD, PhD, N Harris, PhD, and B Szantyr, MD

University of California at Davis, Davis, CA, IGeneX, Inc. Reference Laboratory, Palo Alto, CA and Lincoln, MA.

A previous study indicated that Lyme Disease (LD) symptoms were correlated with night sweat activity presumed to reflect immune system responsiveness to Borrelia burgdorferi (Bb) infection. Fluctuations in reproductive hormones appear to produce an immune response interval (IR) associated with altered Bb activity. We were interested in the possibility that monthly changes in neuroendocrine-immune ovarian activity might influence the appearance or availability of Bb antigens(s) in urine. Multiple urine samples from a single patient with LD were collected daily during 7 consecutive menstrual cycles while antibiotics were being administered.

The portion of the menstrual cycle chosen for study included a 12-13 day period approximating the putative IR, including menses and the days immediately thereafter. Early morning (5-8am), mid-day (11am-3pm), evening (5-8pm) and late night (8-11pm) samples were collected and immediately transferred to BD Urine Vacutainers with preservative. Samples were stored at -76°C. LUATs were performed on each sample (N=285).

Urinary metabolites of progesterone were measured by ELISA throughout three IR(s) selected at random. The case history is particularly interesting because initial LUAT(s), multiple PCR(s), IgG and IgM Western Blot analyses were negative following sample collection at times other than the IR.

Positive LUAT(s) were obtained during the first and all but the second of the 7 IR analyzed. Menstrual cycle stage was significantly correlated with the level of Bb antigen detected in urine. Urines with a positive LUAT (P< 0.05) (N=56) were divided into Group A (collected during the late luteal phase, when urinary progesterone metabolites were highest and began to decline) (N=32) and Group B (collected on the first day of menses or thereafter, when urinary progesterone metabolites were decreased) (N=24).

Excluding all negative LUAT results, mean positive LUAT values were lower prior to menses [41.94 ng/ml + 1.76(S.E.)] compared to mean positive LUAT values obtained on the first day of menses and shortly thereafter [66.42 ng/ml + 6.36 (S.E.)]. This difference is highly significant P < 0.001 and suggests that neuroendocrine-immune-ovarian interaction may influence the availability of Bb antigen in urine. The results of this clinical study also demonstrate that collection of urine for LUAT determinations should include multiple samples obtained on the first day of menses and 3-4 days after that to optimize detection of urinary Bb antigen in women with recurrent menstrual cycles.