Estrogens influence numerous physiological processes in mammals, including reproduction, cardiovascular health, bone integrity, cognition, and behavior. They are implicated in the development or progression of various diseases, such as cancers, osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus, endometriosis, and obesity. Estrogen exerts its effects primarily through the estrogen receptor (ER), which is the basis for many therapeutic interventions. The ER exists in two main forms, ERα and ERβ, with distinct tissue expression patterns. ERα and ERβ are encoded by separate genes, ESR1 and ESR2, and numerous splice variants exist for both receptors. These variants have not been fully characterized, but their functions in normal physiology and disease remain to be elucidated. Selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, exhibit tissue-specific estrogenic activity. Tamoxifen is an ER agonist in bone and uterus but an antagonist in the breast, while raloxifene is an agonist in bone and an antagonist in the uterus. SERMs work by binding to the ER and causing conformational changes that determine which coactivators or corepressors are recruited to the promoter, influencing gene expression and physiological responses. Estrogen plays a role in the development and progression of various cancers, including breast, ovarian, colon, and prostate cancers. ERα is a primary mediator of estrogenic actions in breast cancer, and its expression is associated with more differentiated tumors and a better prognosis. ERβ also has a favorable prognostic role in breast cancer, though its role in tumor progression is controversial. Estrogen also influences ovarian cancer, with ERα and ERβ expressed in different tumor types. ERs may mediate ovarian cancer cell growth, and their role in the development of ovarian cancer remains to be fully understood. In colon cancer, ERβ is the predominant form, and its expression is associated with a protective role in colon tumorigenesis. SERMs such as tamoxifen and raloxifene inhibit the proliferation of colon cancer cell lines, suggesting their potential for prevention and treatment. In prostate cancer, ERβ is more highly expressed than ERα, and its expression is reduced in prostate tumors. ERβ-specific agonists may have a protective role in prostate development and function. Estrogen is implicated in endometrial cancer, with ERα and ERβ playing roles in the development and progression of the disease. Estrogen-dependent endometrial tumors are associated with prolonged exposure to estrogens in the absence of sufficient progesterone. Estrogen regulates skeletal homeostasis and is involved in the development of osteoporosis. ERα and ERβ are present in bone tissues, and their expression is associated with bone health. ER antagonists such as ICI 182,780 reduce bone resorption and promote bone formation. Estrogen hasEstrogens influence numerous physiological processes in mammals, including reproduction, cardiovascular health, bone integrity, cognition, and behavior. They are implicated in the development or progression of various diseases, such as cancers, osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus, endometriosis, and obesity. Estrogen exerts its effects primarily through the estrogen receptor (ER), which is the basis for many therapeutic interventions. The ER exists in two main forms, ERα and ERβ, with distinct tissue expression patterns. ERα and ERβ are encoded by separate genes, ESR1 and ESR2, and numerous splice variants exist for both receptors. These variants have not been fully characterized, but their functions in normal physiology and disease remain to be elucidated. Selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, exhibit tissue-specific estrogenic activity. Tamoxifen is an ER agonist in bone and uterus but an antagonist in the breast, while raloxifene is an agonist in bone and an antagonist in the uterus. SERMs work by binding to the ER and causing conformational changes that determine which coactivators or corepressors are recruited to the promoter, influencing gene expression and physiological responses. Estrogen plays a role in the development and progression of various cancers, including breast, ovarian, colon, and prostate cancers. ERα is a primary mediator of estrogenic actions in breast cancer, and its expression is associated with more differentiated tumors and a better prognosis. ERβ also has a favorable prognostic role in breast cancer, though its role in tumor progression is controversial. Estrogen also influences ovarian cancer, with ERα and ERβ expressed in different tumor types. ERs may mediate ovarian cancer cell growth, and their role in the development of ovarian cancer remains to be fully understood. In colon cancer, ERβ is the predominant form, and its expression is associated with a protective role in colon tumorigenesis. SERMs such as tamoxifen and raloxifene inhibit the proliferation of colon cancer cell lines, suggesting their potential for prevention and treatment. In prostate cancer, ERβ is more highly expressed than ERα, and its expression is reduced in prostate tumors. ERβ-specific agonists may have a protective role in prostate development and function. Estrogen is implicated in endometrial cancer, with ERα and ERβ playing roles in the development and progression of the disease. Estrogen-dependent endometrial tumors are associated with prolonged exposure to estrogens in the absence of sufficient progesterone. Estrogen regulates skeletal homeostasis and is involved in the development of osteoporosis. ERα and ERβ are present in bone tissues, and their expression is associated with bone health. ER antagonists such as ICI 182,780 reduce bone resorption and promote bone formation. Estrogen has