Pre-Onset Changes: Perimenopause
Several years before the onset of menopause, estradiol variations during the cycle are accentuated while progesterone output shows a signi?cant decline despite the persistence of ovulation. The dramatic ?uc-tuations in estradiol are believed to be caused by a reduction in negative feedback in the hypothalamic-pituitary-ovarian axis. Observed FSH elevations re?ect the reduced follicle sensitivity to the trophic effects of FSH and GnRH. The perimenopause is clinically characterized by several manifestations shown below.
Perimenopause-manifestations
Endocrine:
Nervous System:
Metabolism:
In menopause, the fractional adrenal contribution to estrogen activity increases to about 95%. This is due to enhanced conversion of circulating adrenal androgens into estrone in adipose and muscle cells, and to increased fractional conversion of estrone to estradiol. As women progress into the menopausal years, estrone becomes the dominant estrogen.
Why use salivary testing?
Saliva contains the free fraction of the hormones which re?ects the bioactive tissue levels. Free Fractions in saliva correlate more closely with clinical symptoms than total serum hormone levels(which mostly re?ect the bound fraction).
Salivary tests included in the Post Menopause Panels™
Free fractions of salivary: Estrone (E1), Estradiol (E2), Estriol (E3), Progesterone (P1), DHEA, Testosterone (TTF), plus Luteinizing Hormone (LH) & Follicle Stimulating Hormone (FSH).
Three panels are offered:
SHORT POST MENOPAUSE PANEL™ (PHP-1™)
One saliva sample
Panel Includes 6 hormones: E1, E2, E3, P1, DHEA & TTF
Clinical Applications:
- Measurement of hormone baselines
- Monitoring natural hormone replacement therapy (HRT)
- Risk assessment of breast/uterine proliferative diseases and osteoporosis
- Investigation of hormone related libido and emotional vulnerability, vaginal atrophy...and other symptoms as listed in Table 1.
2 saliva samples
1st sample is tested for: E1, E2, E3, P1, DHEA & TTF
2nd sample: Repeat of the 6 hormones
Clinical Applications, of PHP-2™ :
- Irregular Cycles in women where menstrual ?ow is unpredictable, and performing a complete 11 specimen hormone mapping is impractical.
- Perimenopause where hormones ?uctuate causing irregular menstrual flow. In these cases, one specimen is minimally representative of the hormone status, while the 11 specimen mapping is impractical. Note: the first sample is collected any time and then frozen; 20 days later the second sample is collected and both are submitted for testing.
- Therapeutic Monitoring/Hormone Challenge in postmenopausal women, on HRT, or for HRT modification; the PHP-2™ can be used to test hormone baseline levels and efficacy of adjustments in HRT dosage and administration route.
One saliva sample
Panel includes: E1, E2, E3, P1, DHEA, TTF, FSH & LH
Clinical Applications:
- Same as PHP-1™
- To correlate FSH & LH to ovarian hormone response
- More de?nitive diagnosis of menopause in younger women
| PHP-1™ |
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| PHP-2™ |
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* The above panels are not intended for cycling women. Hormone assessment of cycling women from puberty to perimenopause is done by cycle mapping using the 11 sample FHP Panel.™
LH & FSH
The pituitary Luteinizing hormone(LH) & Follicle stimulating hormone(FSH) are gonadotrophins which regulate ovarian function. Both FSH & LH are stimu- lated by hypothalamic GnRH (Gonadotrophin Releasing Hormone). LH has a pulsatile rhythm which varies throughout the cycle. Stress and high cortisol have an adverse effect on LH but not on FSH. Stress renders women more estrogenic and less fertile, and more prone to proliferative diseases.
In perimenopause, there is a growing scarcity in ovarian follicles. LH & FSH production show respectively, a three and seven fold increase over the values found in young menstruating women.
The Expanded PHP-1™ panel simultaneously measures the levels of the two neurohormones FSH & LH and the corresponding concentrations of E2 and P1. Using this panel, progression towards menopause can be more accurately predicted before clinical symptoms set in. Early preventive treatment can be initiated to minimize bone loss, and other somatic symptoms.
Interpretive Advantage
Hormone Balance Analysis
Our Post Menopause Hormone Panel™ report allows you to examine and tailor the balance of the various hormones rather than just replacing one. The PHP1™ & e-PHP1™ routinely include a full page of patient-speci?c interpretive data with risk assessment of proliferative diseases of breast and uterus. Our reports include the Proliferation Potential Indexes™ (PPI™) which correlate the pro-proliferative effects of the three estrogens (E1, E2, and E3) to the anti-proliferative effects of P1 and TTF. Our reports also provide suggestions which help rectify commonly observed hormone imbalances.
Notes: Natural estrogens, including estriol are proliferative; estrogens and their metabolites differ only in the degree of their proliferative potential. Certain estrogen metabolites are falsely promoted as risk markers for breast cancer. A recent multicenter study compared 2/16 Hydroxyestrone ratio in women with breast cancer to a control group of healthy women and concluded that "results do NOT support the hypothesis that the ratio of 2/16 Hydroxyestrone is an important risk factor for breast cancer, or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3…". (Environ Health Perspect. 1998 Mar; 106(3):A126-7)
Case Study: Estrogen Overdosing
Purpose:
To demonstrate the typical estrogen overdosing in post-menopause women in attempts to control somatic symptoms, including hot ?ashes.
Background
The recent Women's Health Initiative Study (JAMA 2002; vol 228(3):321-333) on HRT re-af?rms our long held position that use of synthetic or natural hormone replacement therapies based on symptoms only, and without ongoing monitoring, carries with it grave health risks. Many late and early post-menopausal women are given estrogens of various types to control somatic symptoms, including hot ?ashes. The physicochemical anatomy of a hot ?ash consists of a rapid drop in estrogen coupled with a low progesterone. It is not a dearth in the absolute value of estrogen. Consequently, the continual estrogen treatment, usually prescribed, will overdose the woman while it mitigates somatic symptoms. It blunts the rapid ?uctuations in estrogen by overriding endogenous production.
Patient History & Data
| Age: | 50 yrs Female |
| Last Period: | 3 yrs earlier |
| Bone density changes: | Sub-Clinical or minimal |
| Initial Symptoms: | Hot flashes, emotional and concentration problems |
| Treatment: | Placed on estrogen patch; no hormone monitoring done |
| Outcome: | Control of somatic symptoms, increased aggression and irritability, with tender breasts |
Patient sought further help and a Diagnos-Techs PHP-1™ was ordered.
PHP-1™ Report Summary
| Hormone Levels | Normal Ranges | |
| DHEA: | 6 ng/ml | 3-10 ng/ml |
| Testosterone: | 27 pg/ml | 8-20 pg/ml |
| Estrone: | 35 pg/ml | 26-64 pg/ml |
| Estradiol: | 45 pg/ml | 5-13 pg/ml |
| Estriol: | 42 pg/ml | 14-38 pg/ml |
| Progesterone: | 53 pg/ml | 100-300 pg/ml |
Remarks:
The report showed suf?cient DHEA and testosterone, mild estriol excess, elevated estradiol, and very depressed P1 values. The induced estrogen excess (about 400%) coupled with low progesterone increases breast tissue proliferation, and irritable/aggressive behavior.
Case Management:
Estrogen dose was cut by 65% to prevent override.
20mg BID of sublingual liquid progesterone was given.
Retested 30 days later using the PHP1,™ hormone levels were acceptable and all symptoms were under control.
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Kent, Washington 98032
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