Science of intracrinology in postmenopausal women
Bibliographic record
Abstract
OBJECTIVE: To illustrate the marked differences between classical endocrinology that distributes hormones to all tissues of the body through the bloodstream and the science of intracrinology, whereby each cell of each peripheral tissue makes a small and appropriate amount of estrogens and androgens from the inactive precursor dehydroepiandrosterone (DHEA), DHEA being mainly of adrenal origin. Because only the inactivated sex steroids are released in the blood, influence in the other tissues is avoided. METHODS: Molecular biology has been used for the identification/characterization of the steroid-forming and steroid-inactivating enzymes, whereas steroids have been measured by mass spectrometry-based assays validated according to the US Food and Drug Administration guidelines. RESULTS: Evolution over 500 million years has engineered the expression of about 30 steroid-forming enzymes specific for each peripheral tissue. These tissue-specific enzymes transform DHEA into the appropriate small amounts of estrogens and androgens for a strictly intracellular and local action. Humans, contrary to species below primates, also possess intracellular steroid-inactivating enzymes, especially glucuronyl transferases and sulfotransferases, which inactivate the estrogens and androgens at their local site of formation, thus preventing the release of a biologically significant amount of estradiol (E2) and testosterone in the circulation. Since DHEA becomes the unique source of sex steroids after menopause, serum E2 and testosterone are thus maintained at low biologically inactive concentrations with no activity outside the cells of origin. DHEA secretion, unfortunately, starts decreasing at about the age of 30 at various rates in different women. Moreover, there is no feedback mechanism to increase DHEA secretion when the concentration of serum DHEA decreases. Considering this mechanism is unique to the human, it seems logical to replace DHEA locally in women suffering from vulvovaginal atrophy (genitourinary syndrome of menopause). The clinical data obtained using a small dose of intravaginal DHEA (prasterone) confirm the mechanisms of intracrinology mentioned above which avoid biologically significant changes in serum E2 and testosterone. CONCLUSIONS: The symptoms and signs of vulvovaginal atrophy (genitourinary syndrome of menopause) can be successfully treated by the intravaginal administration of DHEA without safety concerns. This strategy exclusively replaces in the vagina the missing cell-specific intracellular estrogens and androgens. This approach avoids systemic exposure and the potential risks of estrogen exposure for the tissues other than the vagina.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".