I found these two studies that are somewhat related to this topic. I suggest that everyone interested in this matter reads the full studies. Ill bring up few highlights from them.
1.Delayed Puberty and Estrogen Resistance in a Woman with Estrogen Receptor α Variant
http://www.nejm.org/doi/10.1056/NEJMoa1303611#t=articleTop
"The patient is an 18-year-old, adopted white woman who presented at the age of 15 years with absent breast development, primary amenorrhea, and intermittent lower abdominal pain"
"At the time of presentation, laboratory studies revealed a serum estradiol level of 3500 pg per milliliter (normal follicular phase, 11 to 210 [12,848 pmol per liter; normal follicular phase, 40 to 771])"
"To determine whether exogenous estrogens would have an effect, for a total of 5 months, the patient took oral estrogen in the form of conjugated equine estrogen (at a dose of 1.25 mg for 3 months) and micronized estradiol (at doses of 3 and 4 mg per day for 1 month each)."
"Before the initiation of therapy, the patient's serum estradiol levels on immunoassay were invariably elevated, ranging from 750 to 3500 pg per milliliter (2753 to 12,848 pmol per liter) (Table 1). After isotope dilution and LC-MS, results for serum estradiol (2340 pg per milliliter [8590 pmol per liter]) and estrone (1040 pg per milliliter [3847 pmol per liter]) were 10 times the normal preovulatory levels. Serum levels of corticosteroid-binding globulin, sex-hormone–binding globulin, thyroxine-binding globulin, prolactin, and triglycerides were not increased, despite elevated estrogen levels. Gonadotropins remained mildly elevated."
"After isotope dilution and LC-MS, results for serum estradiol (2340 pg per milliliter [8590 pmol per liter]) and estrone (1040 pg per milliliter [3847 pmol per liter]) were 10 times the normal preovulatory levels. Serum levels of corticosteroid-binding globulin, sex-hormone–binding globulin, thyroxine-binding globulin, prolactin, and triglycerides were not increased, despite elevated estrogen levels. Gonadotropins remained mildly elevated."
"Untreated, the patient had a plasma estradiol level that was 10 times the normal value, similar to that of the α-ERKO mouse. Her normal serum levels of sex-hormone–binding globulin, corticosteroid-binding globulin, thyroxine-binding globulin, prolactin, and triglycerides, which are known to be increased by estrogen, provide further evidence of estrogen resistance."
2.Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
http://www.nejm.org/doi/full/10.1056/NEJM199410203311604#t=articleResults
"In this report, we describe a man with estrogen resistance who had osteoporosis, unfused epiphyses, and continuing linear growth in adulthood. He also had elevated serum estrogen concentrations, abnormal gonadotropin secretion, and no target-tissue responses to estrogen therapy."
"The patient did not recall any change in facial structure, thickening or oiliness of the skin, excessive diaphoresis, skin tags, or changes in his voice. He did remember noticing increased pigment in the skin of each axilla starting at the age of 23. Though unmarried, he reported no history of gender-identity disorder. He indicated strong heterosexual interests and had normal functioning, including morning erections and nocturnal emissions."
"he patient had a full beard with early temporal hair loss. There was no thyroid enlargement or gynecomastia. The results of cardiovascular, respiratory, and abdominal examinations were normal. The patient had normal male genitalia with bilateral descended testes, each with a volume of 20 to 25 ml, and a normal-sized prostate gland."
"The serum testosterone concentration was normal, and estradiol, estrone, follicle-stimulating hormone, and luteinizing hormone concentrations were high. "
"On the basis of the hypothesis that primary estrogen resistance might explain the elevated serum estrogen and abnormal serum gonadotropin concentrations, failure of epiphyseal fusion, and possibly insulin resistance, the patient was treated with high-dose transdermal ethinyl estradiol (Estraderm patch system, Ciba, Summit, N.J.) for six months. "
"During estrogen therapy, the patient had no nausea, fluid retention, hypertension, unusual headaches, weight gain, gynecomastia, impotence, or mood alterations. In addition, there was no significant increase in the serum concentration of any estrogen-dependent protein (sex hormone-binding globulin, thyroxine-binding globulin, cortisol-binding globulin, or prolactin) or change in serum gonadotropin concentrations (Table 1). The results of tests of bone turnover were all consistent with active bone demineralization and did not decrease. Finally, total bone mineral density and bone age did not change during estrogen administration."
"The elevated serum estrogen concentrations in this man suggest a compensatory increase in aromatase activity in response to estrogen resistance, and increased aromatase activity could account for the normal concentrations of androgen despite increased secretion of luteinizing hormone. "
Ok. So we had two cases - male and a female - of genetic estrogen resistance. What is relevant to us is the fact that the resistance of the ER caused a marked increase in serum estradiol - in both cases!
If I remember correctly nurselyfe hypothesized that this would not happen in the desensitization of ER.
Another interesting point was that the male participant had a healthy libido and erection quality. Also the male did not show any worsening in his condition when he was treated with estrogen.
So again; I would like to ask from nurselyfe what do you think is the mechanism that would cause a permanent worsening of ones condition - when E2 is elevated.
