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Female Panels

The following five hormones make up the Female Panel. Interactions between these hormones are fundamental to health and, as a consequence, imbalances may negatively impact health.

 

Estradiol (E2)

  • Estradiol is needed for the proper function of progesterone receptors, and maintenance of the right balance between estrogens and progesterone is crucial for hormone health. 
  • High estradiol levels may compete with T3 at T3-responsive gene sites and interfere with the tissue action of T3.
  • High estradiol levels may also increase Thyroid Binding Globulin levels, which binds up free T3 and T4 hormone, resulting in decreased tissue action of T3.
  • Low estradiol levels post-menopause may be a consequence of adrenal dysfunction as postmenopausal production of estradiol comes via conversion from the adrenal hormone DHEA.
 

Progesterone

  • Progesterone may enhance the sensitivity of estrogen receptors. Thus a lack of progesterone could contribute to, or exacerbate, estrogen deficiency symptoms even with a normal E2.
  • Too little progesterone relative to estradiol can result in estrogen dominant symptoms like weight gain at hip, breast tenderness, anxiety, fluid retention and fibrocystic breasts.
 

Progesterone to Estradiol Ratio (Pg to E2)

  • Only endogenous levels of progesterone and estradiol are used in the calculation of the progesterone to estradiol ratios. The most commonly observed range in regularly cycling women in the luteal phase is between 8 and 30, with 15 being the median value (more on last page).
 

Testosterone

  • High testosterone and/or elevated DHEA-S may indicate the presence of polycystic ovary syndrome and/or insulin resistance and metabolic syndrome.
  • Low testosterone levels post-menopause may be a consequence of adrenal dysfunction. After menopause, the adrenal hormone DHEA is the major source of testosterone (DHEA is converted to testosterone).
 

Cortisol

  • Elevated cortisol can interfere with the action of progesterone and testosterone at gene regulatory sites. Consequently, women with normal progesterone and/or testosterone levels may exhibit signs of deficiency when cortisol levels are high. This is called a functional deficiency.
  • High cortisol can induce the enzyme aromatase, which speeds the conversion of testosterone to estradiol; this can result in elevated estradiol levels.
  • Excess cortisol is catabolic for bone and also opposes the action of testosterone, which is anabolic for bone. Thus, significant bone loss may occur with elevated cortisol levels.
  • Elevated cortisol in the evening has been associated with depression. High evening cortisol in breast cancer survivors has been associated with a poorer prognosis.
  • Over time, high cortisol levels may progress to adrenal exhaustion and low cortisol levels.
 

DHEA-S

  • DHEA is stored in the blood mainly in its sulphate form, DHEA-S.
  • Cortisol and DHEA have opposite effects on immune function and insulin regulation.
  • High cortisol levels require more DHEA to be released to balance effects of cortisol. Thus, chronically elevated cortisol can result in a deficiency of DHEA.
  • The ratio of cortisol to DHEA-S increases with age, mostly due to declining DHEA. ZRT Laboratory data shows the ratio at age 20 is 0.6, age 45 is 1.0, age 60 is 1.5, and age 75 is 2.3.
  • Low DHEA-S levels may be associated with hypothyroidism and chronic illnesses such as lupus and rheumatoid arthritis.

 

Restoring Hormone Balance

 

Progesterone-Estradiol Ratio

In women not supplementing with hormones, this ratio may be helpful in detecting relative estrogen excess even when both progesterone and estradiol are within normal limits.
 
  • 95% of regularly cycling women not on hormones have a Pg to E2 ratio of between 8 and 30 (sampled one week prior to onset of menses).
  • A ratio of less than 10 is often associated with estrogen dominant symptoms such as breast tenderness, fluid retention, migraines.
 
Unfortunately, the Pg to E2 ratio is not useful when women are on topical progesterone and/or estrogen. For example, one woman applies 50 mg of progesterone cream and gets a saliva hormone result of 3000 pg/mL. Another woman uses the same dose and tests the same number of hours after cream application, and gets a saliva hormone result of 10,000 pg/mL. This disparity is likely a consequence of the high lipid solubility of progesterone. Depending on body composition, there may be greater or lesser storage of progesterone in fatty tissue, with a resultant wide variability between persons. Thus, the ratio of progesterone to estradiol is a useful index when hormones are produced endogenously, but the utility of the ratio with topical hormones has not been established.

 

Progesterone-Estradiol Balance

If symptoms of estrogen excess (e.g. breast tenderness) are present when an adequate amount of progesterone is given along with estrogen, then decreasing or discontinuing estrogen will generally address the problem. Sometimes switching from oral to transdermal progesterone alleviates estrogen excess symptoms. Occasionally, even when the measured level of progesterone is within range, supplementation with topical progesterone may be useful. If no hormones are being supplemented, then it is a question of addressing the endogenous imbalance: above/high end of range estradiol and/or below or low end of range progesterone. It is important to ensure that other hormones are within range as well; particularly cortisol and testosterone. 
           Results from the Premarin™ only arm of the Women's Health Initiative Study indicates that unopposed oral conjugated estrogens carry an increased risk of stroke. Because there are progesterone receptors throughout the body, not just in the uterus, bio-identical progesterone should always be given with estrogens, even when the patient has had a hysterectomy. Addition of bio-identical progesterone often allows the estrogen dose to be halved, and paves the way for gradual discontinuation of oral estrogens. Once off oral estrogens, a retest of estradiol levels can be performed. If estradiol levels are below range and symptoms are an issue, use of transdermal estradiol (gel, cream or patch) might be worth considering. However, in many cases, bio-identical progesterone is all that is needed.

 

Progesterone Cream

The salivary progesterone level after topical progesterone application is mostly a qualitative measure. In other words, there is no scientific basis for saying that a level of 3000 pg/mL is better than a level of 1000 pg/mL. Nevertheless, there is value in knowing whether the level is above or below range. If the progesterone level is unexpectedly low and clinical response is lacking, perhaps a different carrier (cream or other base) may be needed. Patient compliance should also be investigated if suboptimal clinical results are seen and the progesterone level is below range. If the progesterone level is above range, it may be an indication of excess supplementation. Symptoms such as drowsiness and breast swelling are possible signs of progesterone excess. 
           Although research shows progesterone cream can produce a quiescent endometrium when given with estrogens, there is no human data correlating saliva progesterone levels with progesterone levels in uterine or breast tissue, so maintaining a specific saliva progesterone level is no guarantee of endometrial protection.

 

When To Test?

A single sample mid luteal phase may be representative of the luteal phase overall. A study by Ishikawa concluded that "..a simple measurement of mid-luteal phase progesterone via a single saliva sample taken between days 19 and 21 of the cycle] appeared to be useful for the diagnosis of luteal phase defects.“ Our data shows that for the majority of pre-menopausal women, a single sample taken one week prior to menses is representative of their state of hormone balance. Hormone testing in peri-menopausal women with irregular periods generally shows an estrogen dominant state. In such cases, testing may not be necessary as it generally just confirms the suspected estrogen dominance. Testing in peri-menopause may be useful if new symptoms develop or symptoms are not alleviated by the addition of progesterone. Post-menopausal women are not subject to the same fluctuations in hormone levels as pre-menopausal women.