Aeron LifeCycles Clinical Laboratory applies salivary analysis to the life long hormonal needs of women and men. As a tool for both interest and education, Aeron is compiling a quarterly review for clinicians, which will report short synopses of current findings in hormone science. We have begun here with the latest studies using saliva as well as some of the primers of serum vs. saliva validation.

Elevated Salivary Cortisol in the Evening in Healthy Elderly Men and Women: Correlation with Bone Mineral Density. Researchers from the Medical College of Wisconsin measured morning and evening salivary cortisol in 228 elderly, community-dwelling subjects. Loss of bone mineral density (BMD) is associated with aging as well as hypercortisolemia in both men and women. Authors concluded that salivary cortisol is a simple, non-stressful method for assessing activity of the HPA axis in the elderly population. A major finding of this study was an elevation in the late night nadir in cortisol secretion suggesting that elevated cortisol secretion may contribute to the age-related loss in BMD and that this effect is prevented by HRT.
J Gerontol A Biol Sci Med Sci 1999 Sep; 54(9): M479-83

High Levels of Bioavailable Estrogen Reduce Risk of Cognitive Decline in Women. Because women on estrogen replacement tend to be younger and more educated, and have healthier lifestyles, the role of estrogen in preventing dementia has been unclear. Total serum estrogen levels have not been associated with cognitive function in older women, but this may be because 90% of estrogen in the blood is bound to protein and is not able to cross the blood-brain barrier. These researchers measured non-protein bound serum estrogen (bio-available) and cognitive function in 425 women older than 65 years. Authors report that there was a very clear relationship between level of bio-available estrogen and risk of cognitive decline supporting the idea that estrogen might be protective against dementia.
Lancet 2000; 356:694-695,708-712

Dehydroepiandrosterone (DHEA) rather than Testosterone shows Saliva Androgen Responses to Exercise in Elite Female Handball Players. This French study compared the levels of DHEA and testosterone in a group of 14 elite female handball players to those of 10 sedentary women – before and after exercise. The exercise did not induce significant changes in T and DHEA in either group but a positive correlation between T and DHEA was observed at all points studied. The researchers suggest that measurements of DHEA could serve as a substitute for testosterone measurements to study training responses in elite sportswomen.
Int J Sports Med 2000 Jan; 21(1): 17-20

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol. Objective was to compare salivary, plasma and urinary free cortisol (UFC) measurements between these three populations of women. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting participants by group. However, for plasma cortisol values greater than 500nmol/l the parallelism was lost. Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity.
Eur J Endocrinol 2001 Aug; 145(2): 165-171

Salivary cortisol and DHEA: association with measures of cognition and well being in normal older men, and effects of three months of DHEA supplementation. A clinical trial was conducted in a non-clinical sample of 46 men aged 62-76. Participants received either 50mg of DHEA daily for 13 weeks, followed by placebo for 13 weeks, or the reverse. Levels of salivary cortisol and DHEA were measured at 0800 h and 2000 h prior to each assessment session. They study revealed that controlling for age, a higher morning DHEA was associated with lower confusion while higher evening DHEA was associated with lower anxiety and lower current negative mood in the morning. Conversely, higher morning cortisol and morning cortisol/DHEA ratio were associated with higher anxiety.
Psychoneuroendocrinology 2001 Aug; 26(6): 591-612

Effects of one night of sleep deprivation on hormone profiles and performance efficiency. The Department of Obstetrics and Gynecology, National University of Singapore, recently examined the effects of one night of sleep deprivation by measuring melatonin and cortisol levels using saliva in addition to psychomotor and physical performance tests. They discovered and increase in melatonin but not cortisol in the individuals who slept adequately. Significant increases in melatonin and cortisol were noted on the day after nighttime sleep deprivation. There was no change in physical and psychomotor tests conducted.
Mil Med 2001 May; 166(5): 427-431

Human saliva as a diagnostic specimen. Numerous studies in the past 40 years have shown correlation between serum and saliva levels. Both diurnal and monthly profiles of hormone levels parallel traditional serum patterns. Salivary levels of steroid hormones and other analytes that are protein bound in serum reflect the unbound and active concentration of the hormone. Saliva can be used as a diagnostic specimen not only to obtain information more inexpensively and efficiently than serum, but also to provide information not readily available from serum testing.
J Nutr 2001 May; 131(5): 16215-16255

Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women. It has been suggested because of previous clinical studies, that the circadian nature of melatonin secretion, which is significantly different in obese women, could be of importance in the regulation of bony mass after menopause. The objective of this study was to prove any connection between changes in the melatonin pattern and the circadian metabolism of type I collagen in postmenopausal women with visceral obesity. There results confirmed that alterations in salivary melatonin concentrations might have a protective effect against postmenopausal loss of bone mass.
Neuroendocrinol Lett 2001 Apr; 22(2): 121-127

Actual stress, psychopathology and salivary cortisol levels in the irritable bowel syndrome (IBS). The aim of this study was to measure biological and psychological variables related to the activity of the HPA axis in IBS patients compared to healthy subjects. Salivary cortisol was measured along with 5 self-administered questionnaires. IBS subjects showed significantly higher levels of cortisol in the morning and lower in the evening. Changes in cortisol levels have been shown to be sensitive indicators of psychosocial stress and coping patterns in both laboratory and life situations.
J Endocrinol Invest 2001 Mar; 24(3) 173-177

Saliva as a medium for investigating intra- and interindividual differences in sex hormone levels in premenopausal women. Repeated measurement of ovarian steroids in saliva could provide an advantage in studies estimating long-term sex steroid exposure in premenopausal women, by reducing the measurement error associated with collections of serum or urine samples.
Cancer Epidemiol Biomarkers Prev 2001 Jan; 10(1): 59-64

Salivary testosterone and cognitive ability in children. There are suggestive data, which indicates the link of testosterone levels with specific cognitive abilities in humans. Salivary testosterone levels in children were determined since saliva reflects the free fraction of testosterone directly available for uptake by receptors in the central nervous system. Lower salivary testosterone levels were found in intellectually gifted children of both sexes, and a negative relationship was found between testosterone levels and cognitive abilities in preadolescent children.
Bratisl Lek Listy 2000; 101(8): 470-473

Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of progesterone cream. Serum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both pre and postmenopausal women – consistent with the view that progesterone cream is absorbed and transported through the body.
Clin Endocrinol (Oxf) 2000 Nov; 53(5): 615-620

Salivary estradiol and progesterone levels in conception and nonconception cycles in women: evaluation of a new assay for salivary estradiol. The Department of Obstetrics and Gynecology at Northwestern University Medical School in Chicago took 14 women aged 23-39 with regular cycles. Estradiol and progesterone were measured using saliva and a simultaneous serum sample. The correlation of saliva to the serum sample was .71. Their conclusion was that salivary measurements of estradiol and progesterone may be used as a valid method to assess ovarian function. The sensitivity and precision of the salivary estradiol assay make it comparable with assays of serum estradiol for assessing changes in hormone levels.
Fertil Steril 1999 May; 71(5): 863-8

Serum and salivary testosterone levels in erectile dysfunction. The testosterone levels of 66 men with erectile dysfunction were measured in both saliva and serum. Low salivary (free) testosterone levels were found in 36.4% of patients, while only 10.6% of patients had low serum testosterone levels. Although there is a relationship between serum and salivary testosterone levels (r=0.41, p<0.001), the patients with low salivary testosterone levels have in major part a normal serum total testosterone level. The serum total testosterone level is not a sensitive indicator in detection of hypogonadism. The androgen substitution therapy has a beneficial effect on erectile dysfunction in a significant part of patients. The measurement of free testosterone levels in saliva may have an important role both in diagnosis of diseases characterized by androgen deficiency and hyperandrogenic status.
Orv Hetil. 1998 Aug 23; 139(34): 2021-4

Direct radioimmunoassay of progesterone in saliva. Using a direct radioimmunoassay for progesterone in saliva developed at Northwestern University Medical School, researchers were able to show the correlation between concurrent serum and salivary progesterone concentrations in the luteal phases of menstrual cycles of 48 women was 0.75 (P<0.001). Collection of saliva is a more convenient and less invasive technique for frequent sample collection than phlebotomy, and is useful for monitoring ovulation and assessment of luteal function in women clinically.
J Immunoassay. 1997 May; 18(2): 149-63

Accuracy of salivary estriol testing compared to traditional risk factor assessment in predicting preterm birth. The objective was to compare the predictive accuracy of salivary estriol levels with that of the modified Creasy score for predicting preterm labor followed by preterm delivery. A triple blinded prospective trial was conducted at 8 US centers. Among 601 evaluable patients, serial salivary estriol testing correctly predicted the appropriate outcome 91% of the time while the Creasy score predicted correctly only 75% of the time. Among those in the Creasy high risk group (n=152), use of the salivary estriol correctly predicted the end point 87% of the time compared with only 7.2% by modified Creasy scoring.
Am J Obstet Gynecol 1999 Jan; 180(1 Pt 3): s214-s218

Comparison of the testosterone-to-cortisol ratio values obtained from hormonal assays in saliva and serum. The Department of Endocrinology at the Institute of Sport in Poland, determined testosterone (T) and cortisol (C) in serum and saliva simultaneously from a group of athletes in order to determine the T:C ratio, the relationship between them and whether it can be used as a measure of the anabolic-catabolic index. The mean salivary ratio was nearly 3-fold lower than that obtained for serum but they were strongly correlated (r=0.874, p<0.001). The slope of the saliva-serum regression line was significantly lower for serum cortisol concentrations over 600 nmol/L than for concentrations below that value. It was concluded that the salivary T:C ratio, based on values reflecting the levels of biologically active fractions of T and C in circulation, is a better measure of metabolic equilibrium conditioned by those hormones than the ratio obtained in serum.
J Sports Med Phys Fitness. 1997 Mar; 37(1): 50-5

Autonomic cardiovascular regulation in obesity. A cross-sectional correlation study was done to establish the relationship between obesity and autonomic regulation as well as salivary cortisol levels. Three patient cohorts were samples covering ranges of body mass index, and stratified for age, sex and menopausal status. They concluded that with increasing weight, no overstimulation was found but a depression in sympathetic and parasympathetic activity together with a significant reduction in baroreflex functioning and in salivary cortisol levels.
J Endocrinol. 2000 Jan; 164(1): 59-66

Salivary excretory pattern of testosterone in substitutive therapy with testosterone enanthate. The objective of this study was to determine salivary and serum testosterone (T) levels by a RIA method after a single injection of 250mg IM of commercially available T enanthate. Saliva samples were taken before the injection and then daily until day 7 and then every other day until day 28. Serum was collected before and then five times in the month following the injection. It was concluded than T salivary concentrations may be applied to assess the effectiveness of T substitutive therapy in hypogonadal men and that they could replace serum in the monitoring of this type of therapy.
Fertil Steril. 1994 Jan; 61(1): 125-8

The return of postpartum fertility monitored by enzyme-immunoassay for salivary progesterone. A longitudinal study in which daily salivary progesterone and estrone were measured by solid-phase enzyme-immunoassays was performed in 30 postpartum women to monitor the return of ovarian activity. Recovery was slower in lactating women compared with non-lactators. They concluded that salivary progesterone measurements were useful for monitoring the return of ovarian activity postnatally.
Gynecol Endocrinol. 1992 Mar; 6(1): 37-48

Salivary progesterone concentrations after tubal sterilization. The objective of this study was to find out if ovarian endocrine function is hampered by laparoscopic tubal sterilization. They measured the salivary progesterone levels of 55 women undergoing a laparoscopic tubal sterilization with Hulka or Filshie clips. Saliva was collected every morning for 3 menstrual cycles preceding the procedure and 3 and 12 months after. The results showed that progesterone secreted in the luteal phase declined slowly after the sterilization, resulting in the lowest values 1 year after the procedure. Although the peak progesterone secretion seemed to have started to recover at 12 months, it was still significantly less than before surgery.
Obstet Gynecol 1996 Nov; 99(5): 792-796