Analysis of information sources in references of the Wikipedia article "Polyestradiol phosphate" in English language version.
Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
The castrate level was defined as testosterone being less than 50 ng/dL (1.7 nmol/L), many years ago. However contemporary laboratory testing methods showed that the mean value after surgical castration is 15 ng/dL [1]. Thus, recently the level is defined as being less than 20 ng/dL (1 nmol/L).
The polymer of estradiol or estriol and phosphoric acid has an excellent depot action when given intramuscularly (polyestriol phosphate or polyestradiol phosphate) (Table 16). Phosphoric acid combines with the estrogen molecule at C3 and C17 to form a macromolecule. The compound is stored in the liver and spleen where the estrogen is steadily released by splitting off of the phosphate portion due to the action of alkaline phosphatase. [...] Conjugated estrogens and polyestriol and estradiol phosphate can also be given intravenously in an aqueous solution. Intravenous administration of ovarian hormones offers no advantages, however, and therefore has no practical significance. [...] The following duarations of action have been obtained with a single administration (WlED, 1954; LAURITZEN, 1968): [...] 50 mg polyestradiol phosphate ~ 1 month; 50 mg polyestriol phosphate ~ 1 month; 80 mg polyestriol phosphate ~ 2 months.
[...] In a study with parenteral estrogen therapy of patients with metastatic breast cancer, 14/24 patients obtained an objective response (including patients with stable disease >6 months) [13]. The only side effect reported was bleeding from a hyperplastic endometrium.
Treatment with estrogen has the highest incidence of gynecomastia, at 40 – 80%, anti-androgens, including flutamide, bicalutamide and nilutamide, are next, with a 40 – 70% incidence, followed by GnRH analogs (goserelin, leuprorelin) and combined androgen deprivation, both with incidences of 13% each.
Polyestradiol phosphate (PEP) has been demonstrated to have inhibitory activity against hyaluronidase, acid phosphatase and alkaline phosphatase (Fernö et al., 1958).
Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.
More than 50 years ago, orally given estrogen was already used in the treatment of prostate cancer. Due to cardiovascular side-effects with a high morbidity of 25%, this treatment has not become standard. Recent investigations show that parenteral application reduces the risk of cardiovascular side-effects, because it avoids the first passage through the liver with high concentrations of estrogen which normally occur after oral application. Therefore, an increased synthesis of so-called "steroid-sensitive" liver proteins, such as coagulation factors (especially factor VII) can be avoided. This newer parenteral estrogen application shows encouraging results of a cheap and effective hormonal therapy with a low rate of side-effects in patients with prostate cancer.
[...] In a study with parenteral estrogen therapy of patients with metastatic breast cancer, 14/24 patients obtained an objective response (including patients with stable disease >6 months) [13]. The only side effect reported was bleeding from a hyperplastic endometrium.
Treatment with estrogen has the highest incidence of gynecomastia, at 40 – 80%, anti-androgens, including flutamide, bicalutamide and nilutamide, are next, with a 40 – 70% incidence, followed by GnRH analogs (goserelin, leuprorelin) and combined androgen deprivation, both with incidences of 13% each.
Polyestradiol phosphate is a polymeric ester of estradiol -17 beta and phosphoric acid. The large molecule has very weak estrogenic properties but is a strong inhibitor of several enzymes, e.g. acid and alkaline phosphatases and hyaluronidase.
Polyestradiol phosphate (PEP) has been demonstrated to have inhibitory activity against hyaluronidase, acid phosphatase and alkaline phosphatase (Fernö et al., 1958).
[...] In a study with parenteral estrogen therapy of patients with metastatic breast cancer, 14/24 patients obtained an objective response (including patients with stable disease >6 months) [13]. The only side effect reported was bleeding from a hyperplastic endometrium.
Treatment with estrogen has the highest incidence of gynecomastia, at 40 – 80%, anti-androgens, including flutamide, bicalutamide and nilutamide, are next, with a 40 – 70% incidence, followed by GnRH analogs (goserelin, leuprorelin) and combined androgen deprivation, both with incidences of 13% each.
