Managing Pain in the Presence of Autoimmune Disease
Sahar Swidan, Matthew Bennett in Advanced Therapeutics in Pain Medicine, 2020
Now why use estriol and not just estradiol alone? Estriol is the weakest of the three estrogens the body produces but has many functions in the body. It is not strong enough to prevent cardiovascular disease and keep the bones strong though, thus the 20% estradiol. Estradiol is powerful enough to produce improvement in cardiovascular risk and bone health but can turn into estrone excessively.80 Topical estradiol is available in patch form, but great caution needs to be exercised because of its tendency to convert excessively to estrone. Estrogen should never be used without also using progesterone. For one reason, they work together for many processes. Progesterone helps to make good strong bones, and estrogen prevents excessive loss of bone. Also, we do not want excessive estrogen impact on breast tissue without progesterone to protect the breast.81 The same goes for estrogen dominance and its negative impact on autoimmune disease prevention or reversal.74
Autocrine and Paracrine Actions of Prolactin in Uterine Neoplasia
Nagasawa Hiroshi in Prolactin and Lesions in Breast, Uterus, and Prostate, 2020
Estrogens in postmenopausal women arise mainly by the aromatization of adrenal androgens in the peripheral tissue.49 Several investigations have demonstrated increased circulating levels of estrone and its precursors, androgens, in postmenopausal patients with endometrial adenocarcinoma.50-52 MacDonald and Siiteri53 have presented a hypothesis which relates the estrogenic hormonal milieu of near-exclusive estrone production to the occurrence of endometrial neoplasia. As to the factors regulating estrogen formation in the peripheral tissue, Simpson et al.54 first reported the stimulation of estrone production by glucocorticoids in human adipose tissue in vitro. Recently, Folkerd and James55 provided the confirmatory results. Further, they presented evidence that PRL potentiated the stimulatory effect of dexamethasone on aromatase activity in human adipose tissue. The synergistic effect of PRL with dexamethasone on aromatiase activity was also found in the human choriocarcinoma cell line ENAMI.56
Cancer of the Breast
Jennifer L. Kelsey, Nancy G. Hildreth in Breast and Gynecologic Cancer Epidemiology, 2019
The etiologic role of estrone has also been considered. A role for estrone would not be inconsistent with the estriol ratio hypothesis since high levels of estrone would tend to occur when the estriol ratio is low. Estrone is known to be carcinogenic in animals,248,249 and is believed to be involved in the etiology of endometrial cancer in humans (see Chapter 3). In postmenopausal women, estrone is the major circulating estrogen290 and is primarily formed by the conversion in adipose tissue of a precursor, androstenedione, which is secreted from the adrenal gland.291,292 The higher rate of conversion of androstenedione to estrone in obese women than in nonobese women293,294 could explain the increased risk of breast cancer associated with obesity in postmenopausal women.
Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause
Published in Expert Review of Clinical Pharmacology, 2022
Céline Gérard, Jean-François Arnal, Maud Jost, Jonathan Douxfils, Françoise Lenfant, Coralie Fontaine, René Houtman, David F. Archer, Robert L. Reid, Rogerio A. Lobo, Ulysse Gaspard, Herjan J.T. Coelingh Bennink, Mitchell D. Creinin, Jean-Michel Foidart
Four natural estrogens are found in human species over the course of life (Figure 1A). The names and abbreviations reflect the number of hydroxyl groups present on the 4-ring backbone, as is similar for all hormones. Estrone (E1) is present throughout life and is considered the primary estrogen during the menopausal years in women. Estradiol (E2), produced by the ovaries, is the primary estrogen during the reproductive years. Estriol (E3) is produced naturally by the placenta and is the major estrogen during pregnancy. Lastly, estetrol (E4) is the estrogen of fetal life, produced by the fetal liver, and present only during pregnancy with relatively high levels in the fetus and lower levels in the maternal circulation. Interestingly, whereas E1, E2, and E3 are found in other mammalian species, E4 is primarily only found in humans, present as early as 9 weeks of gestation. Some higher order mammals have limited levels of E4 present but only in the last few weeks of gestation. The unique role of E4 in humans, compared to lower-order mammals, is still not understood.
The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects
Published in Climacteric, 2022
A. Mandelli, E. Tacconi, I. Levinger, G. Duque, A. Hayes
Estrogens are a class of steroid hormones derived from cholesterol. The three naturally produced molecules are 17β-estradiol, estrone and estriol, with the former being the main circulating form [13]. Estrogens are mainly produced in the ovaries by theca and granulosa cells, starting from androgens until the last step of aromatization by the aromatase enzyme. This enzyme has been found to be also expressed in bone [14,15] and muscle [16]. Estrone and estriol are instead formed in the liver from estradiol. Estrogen production varies during the menstrual cycle and lifespan of a woman, reaching its lowest concentration during menopause (20 pg/ml) [17]; in postmenopausal women, estrone is the most predominant molecule. In the plasma, estrogens bind to the sex hormone binding globulin and with less affinity to albumin; only 2–3% circulates free [13].
Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review
Published in Expert Opinion on Drug Delivery, 2020
The human estrogens include estrone (E1) and 17 β estradiol (E2), both of which are produced in the ovary, estriol (E3) which is produced by the placenta during pregnancy and estretol (E4) also found only in pregnancy. Of the endogenous estrogens, E2 has the greatest binding affinity for the estrogen receptors. In premenopausal women, the majority of circulating E2 (70 to 500µg/day) is derived from the dominant ovarian follicle through the aromatization of testosterone with only a small amount of estradiol resulting from peripheral conversion of estrone [28]. Before menopause, E2 circulates at 1.5 to 4 times the serum level of E1. The onset of menopause heralds the cessation of ovarian follicular function and a change in the serum estradiol:estrone ratio. In postmenopausal women, the primary circulating estrogen is estrone (E1) which is derived mainly from peripheral aromatization of adrenal androstenedione in muscle and fat [34].