Spring 2003

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.

Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology. The objective was to determine the endometrial response and bleeding patterns in postmenopausal women taking sequential combined hormone replacement regimen either orally or transdermally. 72 postmenopausal women with amenorrhea of 6 months or longer with FSH and estradiol levels in the postmenopausal range and normal endometrium were included. The rates of adequate progestational response (secretory or atrophic) were 83.8% and 82.9% in the oral and transdermal hormone replacement groups, respectively (p>0.05). Sequential combined transdermal hormone replacement therapy is as effective as oral therapy in preventing the development of endometrial hyperplasia. Satisfactory control of bleeding is achieved with both regimens.
Arch Gynecol Obstet 2001 Nov;265(4):209-13

Changes in rates of salivary estriol increases before parturition at term. The objective of this study was to characterize the increases of salivary estriol concentrations before the onset of labor at term. Salivary estriol concentrations were measured weekly on 16 healthy pregnant women from 30 weeks gestation until the time of parturition and delivery. The median salivary estriol concentration profile revealed a nonlinear rise beginning from 30 weeks gestation (0.89ng/ml) until term (2.70ng/ml). At 35 weeks’ gestation the salivary estriol concentration median value increased sharply (50-93% increase). The late pregnancy rise in salivary estriol concentrations showed distinct patterns that tended to be characteristic of the length of pregnancy.
Am J Obstet Gynecol 2001 Jan;184(2):123-30

Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. This 2-year, double masked, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy in preventing bone loss in postmenopausal women of two doses of transdermal 17 beta estradiol delivered by a matrix patch, compared with placebo. 160 healthy, hysterectomized postmenopausal women aged 40-60 with serum estradiol levels <20pg/ml. Treatment arms were estradiol 100 mcg/day, 50 mcg/day and placebo. Estradiol delivered by the E-50 matrix patch effectively reversed bone loss in hysterectomized postmenopausal women with few side effects. The marginal additional gain in BMD with the higher dose may be offset by a more important side effect profile.
Osteoporos Int 2002;13(2):176-83

Effects of continuous combined hormone replacement therapy on inflammation in hypertensive and/or overweight postmenopausal women. With the hypothesis that hypertensive and/or overweight women may be less likely to realize cardiovascular benefits from estrogen, researchers administered micronized progesterone (100 mg MP) or medroxyprogesterone acetate (2.5 mg MPA) with conjugated equine estrogen (0.625 mg CEE) daily during 2 months to 35 hypertensive and/or overweight postmenopausal women with a randomized, double blind, crossover design. With significant changes of lipoproteins, CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha levels……but not C-reactive protein and fibrinogen levels. Of note, there were no significant differences between each therapy regarding these effects.
Arterioscler Thromb Vasc Biol 2002 Sep 1;22(9):1459-64

Effects of transdermal and oral estrogen replacement therapy on C-reactive protein levels in postmenopausal women: a randomized, placebo-controlled trial. To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), a 15 month study was conducted on 152 healthy hysterectomized postmenopausal women. They were given a placebo, transdermal estradiol 50mcg, or oral estradiol 1mg combined with gestodene 25mcg for 13 cycles followed by 4 cycles of placebo for each group. Oral estradiol significantly increased CRP levels. This change was larger than the increase found during oral estradiol+gestodene. Transdermal estradiol did not affect CRP levels
Thromb Haemost 2002 Oct;88(4):605-10

Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women. Previous studies have alluded to a role for both oestradiol and progesterone in the secretion of leptin from fat cells in the human, although direct evidence has yet to be obtained. This study was to assess serum leptin concentrations in normally cycling women receiving exogenous oestradiol and progesterone. Normally cycling women were investigated in an untreated cycle, treated with oestradiol, and a cycle treated with oestradiol and progesterone. A skin patch was used to deliver the oestradiol and progesterone was given intravaginally. In the oestradiol + progesterone cycles, leptin concentrations correlated significantly with oestradiol and progesterone concentrations, but not with FSH and LH concentrations. These results show that leptin secretion can be stimulated in women by the administration of oestradiol plus progesterone. This may explain the increased concentrations of leptin during the luteal phase of the normal menstrual cycle
Hum Reprod 2001 Sep;16(9):1827-32

The clinical usefulness of salivary progesterone measurement for the evaluation of the corpus luteum function. This study was designed to construct reliable daily salivary progesterone profiles throughout the luteal phase to accurately evaluate the corpus luteum function. Furthermore, they investigated the clinical relevance of simple midluteal salivary progesterone estimation for the diagnosis of luteal phase insufficiency by determining the diagnostic efficiency and cutoff values. A total of 121 women were divided into 3 groups; normal luteal function, luteal phase insufficiency, and unclassified group. The cutoff values of 189 pmol/l in the midluteal phase yielded a sensitivity of 78% and a specificity of 76.5%. Their results suggest that a simple estimation of midluteal salivary progesterone appeared to be useful for the diagnosis of luteal phase defects.
Gynecol Obstet Invest 2002;53(1):32-7

Salivary progesterone levels and rate of ovulation are significantly lower in poorer than better-off urban-dwelling Bolivian women. Agriculturists in less-developed countries (LDC) have lower progesterone levels than urban industrialized populations. However, it is unknown if urban LDC populations are also relatively lower. Researchers studied whether urban Bolivia samples-poorer (Bol-p) and better-off (Bol-b) have lower progesterone than a Chicago (USA) sample, and whether progesterone and rates of ovulation are lower in Bol-p than in Bol-b. Serial salivary samples were taking during two menstrual cycles. Progesterone levels are lower in the Bolivian samples and higher in the Bol-b than Bol-p; ovulation rate is greater in Bol-b than Bol-p. Principal components representing body size and progesterone levels are positively correlated.
Hum Reprod 2002 Jul;17(7):1906-13

Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women.  The school of medicine at UCSF compared the mood and somatic effects during the initial 2 months of medroxyprogesterone acetate (MPA) or progesterone combined with conjugated equine estrogen (CEE) in early postmenopausal women. They studied 23 non-depressed, early postmenopausal women (average age 52.5 years) who completed a 91 day, single blind pilot study using 2 week cycles of different HRT combinations off CEE, CEE+MPA, CEE+MP – with a week of placebo in-between. MPA users reported more vaginal bleeding and breast tenderness than progesterone users. In contrast with the widely held belief among psychiatrists that progesterone depresses mood, neither the MPA or MP used in normal, nondepressed women showed this effect in this study.
Menopause 2002 Jul-Aug;9(4):253-63

Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Generally, androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti-inflammatory hormones. Low levels of gonadal androgens and adrenal androgens, as well as lower androgen/estrogen ratios, have been detected in the saliva of both male and female rheumatoid arthritis patients. Therefore, sex hormone balance is still a crucial factor in the regulation of immune and inflammatory responses, and the therapeutical modulation of this balance should represent part of advanced biological treatment for rheumatoid arthritis and other autoimmune rheumatic diseases.
Ann N Y Acad Sci 2002 Jun;966:131-42

Monthly patterns of testosterone and behavior in prospective fathers. The individual time patterns of salivary testosterone of adult healthy men, self-reported sexual behavior and their co-occurrence with regular weekly or monthly intervals were studied. 27 volunteer males (mean age 33 years) collected daily saliva over a period of 90 days. Peak hormone levels occurred around weekends in the majority of the males. The 28-day monthly interval coincided with testosterone peaks only in those of the paired men who reported a current wish for children, but not in unpaired men or in those who did not wish to have children with their current partner
Horm Behav 2002 sep;42(2):172-81

Testosterone, sexuality and antisocial personality in rapists and child molesters: a pilot study. Morning and afternoon levels of saliva testosterone levels in Finnish imprisoned rapists (n=10) and child molesters (n=10) were compared to those in random selected control subjects (n=31). In the sexual offenders, a summed ASP (antisocial personality disorder) index was positively correlated with mean saliva testosterone. Self reported sexual activity was significantly related to testosterone in both rapists and child molesters but not in control males.
Psychiatry Res 2002 Jul 31;110(3):239-47

The circalunar cycle of salivary testosterone and the visual-spatial performance. This German study describes the infradian variations of testosterone and the correlation between salivary testosterone levels and spatial abilities in young healthy volunteers of both sexes. Testosterone levels in saliva were determined in 53 young adult male and female volunteers (mean age 20.89). Samples were collected once on 22 subjects and daily for 30 days on 31 subjects. This data and the results of the visual-spatial tests as well as the circalunar cycle in relationship to the testosterone levels was analyzed. A positive correlation of salivary testosterone level and the visual spatial performance test in woman and a negative dependence in men was found. The levels of testosterone between the high female and low male range seem to be associated with the best spatial ability performance in adults.
Bratisl Lek Listy 2002;103(2):59-69

Nighttime salivary cortisol: a useful tests for the diagnosis of Cushing’s syndrome. Clinical features such as weight gain, depression, hypertension, and menstrual irregularities, although common in the general population, may raise the possibility of Cushing’s syndrome. Up to 30% of urine cortisol and dexamethasone suppression screening tests may return an incorrect result, suggesting that better tests are needed. This study evaluated the utility of nighttime salivary cortisol measurement as a screening test for Cushing’s syndrome. An assay specific inpatient 24-h salivary cortisol or an outpatient bedtime salivary cortisol greater than 550 ng/dl identified 93% of patients with Cushing’s syndrome (confidence interval, 89-98%) and excluded all individuals without this disorder.
J Clin Endocrinol Metab 2002 Oct;87(10):4515-21

Elevation of the cortisol-dehydroepiandrosterone ratio in drug-free depressed patients. Elevated basal cortisol levels are a feature of depressive illness and cause deficits in learning and memory. Cortisol and DHEA were measured in saliva samples from 39 patients with unipolar depression who had been medication free for at least 6 weeks and 41 healthy comparison subjects. The cortisol-DHEA ratio was significantly higher in the depressed patients than in the control subjects. Cortisol-DHEA ratios from saliva samples taken at 8:00pm correlated positively with length of current depressive episode.
Am J Psychiatry 2002 Jul;159(7):1237-9

Effects of rapid tryptophan depletion on salivary and plasma cortisol in Alzheimer’s disease and the healthy elderly. Effects of lowering brain serotonin on salivary and plasma cortisol were assessed in patients with dementia of Alzheimer type (DAT) and in control subjects. A double-blind, cross-over design involving administration of two nutritionally balanced amino acid mixtures with or without tryptophan was used. Salivary and plasma cortisol was measured at intervals before and after the drink. In subjects with DAT and healthy elderly subjects, acute tryptophan depletion had no effect on cortisol secretion.
>J Psychopharmacol 2002 Mar;16(1):73-8

Slowing the progression of cognitive decline in Alzheimer’s disease using mifepristone. High circulating levels of glucocorticoid hormones adversely affect cognition. Previous studies in the elderly have reported that subjects with mid range cortisol levels outperformed subjects with high cortisol levels on assessments of memory and attention. This study examined the efficacy of mifepristone (a glucocorticoid-antagonist) in decelerating the rate of cortisol-related cognitive decline in subjects with mild to moderate Alzheimer’s disease (AD). Salivary and plasma cortisol levels were taken at each visit to determine HPA axis activity. The placebo of this study investigated whether subjects with high baseline cortisol levels experience greater declines in cognitive impairment over time relative to subjects with AD who have low baseline cortisol levels.
J Mol Neurosci 2002 Aug-Oct;19(1-2):201-6

Ultrasound measures of bone and the diurnal free cortisol cycle: a positive association with the awakening cortisol response in healthy premenopausal women. This study examined the relationship between characteristics of the diurnal pattern of salivary free cortisol concentration and ultrasound (US) measures of bone in premenopausal women. Subjects were 36 healthy, eumenorrhoeic, nonsmoking women – 30.9 mean age. Saliva samples were collected upon waking and 10, 20, 30, 120, 240, and 600 minutes thereafter. Calcaneal broadband ultrasonic attenuation and speed of sound were significantly associated with cortisol 0 and 30 min after awaking. A high peak in cortisol following awakening was associated with higher US measures of bone in healthy premenopausal women. This finding suggests the possibility that diurnal variation in cortisol may have a role in bone metabolism.
Calcif Tissue Int 2002 Jun;70(6):463-8

Effect of exercise at three exercise intensities on salivary cortisol. Changes in cortisol concentration in response to exercise at 3 different intensities were quantified. No significant differences in cortisol concentration were noted among resting, low-, and moderate-intensity exercise. Exercise <40 minutes elicited no significant differences at any intensity. The data indicated that only exercise of high intensity and long duration results in significant elevation of salivary cortisol.
J Strength Cond Res 2002 May;16(2):286-9