Adequate levels and an appropriate balance of the steroid hormones (estrogens, progesterone, testosterone, DHEA, and cortisol) are necessary for maintaining optimal health and well being in both females and males. This family of steroid hormones supports a wide range of essential physiological functions. Variation in these hormones plays a large role in the changes seen in life cycle events such as aging. There has been interest in supporting such hormone activity by dietary changes, herbal use, and medications. Quantitative measurement of steroid hormones in saliva allows a non-invasive way to establish a baseline hormone levels and monitor the impact of intervention.

Estrogen

• Estradiol
  Estradiol is the most potent estrogen of a group of endogenous estrogen steroids which includes estrone and estriol. In women estradiol is responsible for growth of the breast and reproductive epithelia, maturation of long bones and development of the secondary sexual characteristics. Estradiol is produced mainly by the ovaries with secondary production by the adrenal glands and conversion of steroid precursors into estrogens in fat tissue.
  
  During the early part of the menstrual cycle, estradiol levels remain nearly constant. This is followed by a rapid increase reaching a peak the day before or the day of the Leutinizing Hormone (LH) surge (ovulation). It is generally believed that the rise in estradiol is the factor which triggers LH release. Following ovulation there is a drop in estradiol followed by a second rise which corresponds with the formation of the corpus luteum.
  
  At menopause, estrogen concentrations in the body fall to low levels. This decrease is often accompanied by vascular instability (hot flashes and night sweats), a rise in incidence of heart disease, and an increasing rate of bone loss (osteoporosis), Estrogen replacement for alleviation of menopausal symptoms or to prophylax against heart disease and osteoporosis has become very common.
  
  Estradiol levels are used to assess fertility, amenorrhea and precocious puberty in girls. Measurement of estrogen levels is also useful to monitor and titrate replacement therapy especially when the endpoints are long term health (reduction in heart disease and osteoporosis) rather than the immediate relief of symptoms.
  
  
• Estrone
  Estrone is one of the three naturally occurring estrogens, the others being estradiol and estriol. Estrone is produced primarily from androstenedione originating from the gonads or the adrenal cortex. In premenopausal women, more than 50% of the estrone is secretd by the ovary. In prepubertal children, men and non-supplemented postmenopausal women the major portion of estrone is derived peripheral tissue conversion of androstenedione. Interconversion of estrone and estradiol also occurs in peripheral tissue. Bioassay data indicate that the estrogenic action is much les than estradiol. Estrone is a primary estrogenic component of several pharmaceutical preparations, including those containing conjugated and esterified estrogens. In premenopausal women estrone levels generally parallel those of estradiol. After menopause estrone levels increase, possibly due to increased conversion of androstenedione to estrone.
   
• Estriol
  Estrol is one of the three major naturally occurring estrogens, the others being estradiol and estrone. Estriol is produced almost exclusively during pregnancy and is the major estrogen produced in the normal human fetus. During pregnancy the production of estriol depends on an intact maternal-placental-fetal unit. Fetal-placental production of estriol leads to a progressive rise in maternal circulating levels reaching a late-gestational peak several orders of magnitude greater than non-pregnant levels. Estriol has been suggested to be less carcinogenic than estradiol and estrone in animal studies. It has been shown that at doses effective for the relief of postmenopausal symptoms, estriol does not induce endometrial proliferation to the extent as the other estrogens. Topical estriol has also been used for the relief of postmenopausal genital atrophic changes and urinary incontinence.
  
  
• Estrogen metabolism
  Monitoring estrogen metabolism is the next step in patient care and prevention of diseases. The goal of estrogen metabolism monitoring is to assess and reduce potential risk of disease as much as possible by monitoring which estrogen metabolites are being produced, the relationship between the metabolites, and how replacement therapy effects these metabolite levels.
  
  The three most prevalent metabolites of estradiol and estrogen are 2 (OH) estrone, 4 (OH) estrone and 16 alpha (OH) estrone. 2 (OH) estrone are considered protective as they have been found to be powerful antioxidants, protecting against iron induced lipid peroxidation. 4 (OH) estrone is considered a free radical generator and increased levels may induce the production of super oxide free radicals. 16 (OH) estrone is considered genotoxic and may be important in predicting cancer of the breast. The ratio between 2 (OH) and 16 (OH) estrone is considered an important indicator of cancer risk with increase levels of 16 (OH) being beneficial in preventing breast cancer.

Perimenopause
Perimenopause is the time leading up to and immediately following menopause and literally means “surrounding menopause”. Technically, menopause is an event that occurs twelve months after a women’s last menstrual cycle. Generally occurring during a women’s forties, perimenopause can begin as early as age 35 and can last anywhere from 2 – 7 years.

Over a rather lengthy period of time sex steroids hormones first begin to fluctuate, then fluctuate wildly, and then decline causing a number of physiological changes and symptoms. Ranging from subtle to dramatic, these often unexpected physical and emotional changes, such as hot flashes, insomnia, decreased libido and mood swings can be disconcerting. Symptoms of perimenopause are highly individual as you will see from the following chart.

• Progesterone
  Progesterone is a steroid hormone synthesized from cholesterol and is important as an intermediate in the pathway to cortisol via pregnenolone, estrogens and testosterone. Progesterone induces the cyclic changes in the endometrium that allow implantation of the fertilized ovum. Progesterone is also responsible for maintenance of the uterus during pregnancy, suppression of uterine contractions until just prior to parturition and preparation of the breasts for lactation.
   
  During the second half luteal phase progesterone levels increase sharply for a maximum of 5 – 10 days. If a women is not pregnant a steep decline in these levels is seen about days prior to the menstrual period.

In post menopausal it has been shown that a combination of progesterone plus estrogen provides an optimal hormonal profile for prevention of cardiovascular disease, osteoporosis and uterine protection. Progesterone has also been suggested to alleviate the symptoms of PMS.

Testosterone
Testosterone is an anabolic steroid synthesized primarily by the testes in males, the ovaries in females, and adrenal glands in both sexes. Testosterone is synthesized from androstenedione, a product of dehydroepiandrosterone (DHEA) and progesterone, both of which are products of pregnenolone and cholesterol.

At puberty, and throughout most of the reproductive years, approximately 10 – 20 times more testosterone is synthesized in males than in females. In males at puberty, the much higher level of testosterone is responsible for the development of male external genitalia and secondary hair patterns, stimulation of spermatogenesis, stimulation of anabolic activity leading to increased muscle mass and behavioral changes. In pubescent females, testosterone effects are more subtle but equally important for proper musculoskeletal development, general anabolic activity, and libido. In both sexes, testosterone enhances aerobic metabolism and increases protein synthesis.

Testosterone decreases with age in both men and women. Testosterone replacement has been used to treat some postmenopausal symptoms, especially lack of libido in women who have received chemotherapy. It has also been used effectively in the treatment of anemia and the weakness and muscle wasting syndrome associated with AIDS. Recent research on the affects of testosterone on aging demonstrates a gain in lean body mass and a possible decline in bone loss when used in elderly patients.

Since testosterone can have significant side effects (acne, hirsutism, deepening voice, and clitorimegaly) measurement of levels can help define a deficiency and allow titration of therapy without risking significant toxicity.