Dr. Mache Seibel is a global leader in women’s wellness and menopause. He is a 20 years member of the Harvard Medical School Faculty and Editor of The Hot Years Magazine, Creator of Menopause Breakthrough System and recipient of multiple awards including the Best Doctors in America and the Media Award from the North American Menopause Society. Dr. Mache has been featured in People magazine, Discover magazine, Today, MSNBC, hosted PBS specials and appeared on many other media outlets. He is also a frequent keynote speaker for numerous organizations, businesses, and conferences. Dr. Mache and his wife live in Boston, Massachusetts.
However, de novo resistance to endocrine therapy undermines the efficacy of using competitive inhibitors like tamoxifen. Hormone deprivation through the use of aromatase inhibitors is also rendered futile.  Massively parallel genome sequencing has revealed the common presence of point mutations on ESR1 that are drivers for resistance, and promote the agonist conformation of ERα without the bound ligand . Such constitutive, estrogen-independent activity is driven by specific mutations, such as the D538G or Y537S/C/N mutations, in the ligand binding domain of ESR1 and promote cell proliferation and tumor progression without hormone stimulation. 
Less common side effects are bleeding gums, breakthrough vaginal bleeding, vaginal spotting, changes in menstrual flow, painful menstruation. pre-menstrual syndrome, no menstrual period during and after estrogen use, enlargement of uterine fibroids, vaginal infection with Candida, a cystitis-like syndrome, mild diarrhea, jaundice or yellowing of the skin or whites of the eyes, rash, loss of scalp hair, and development of new hairy areas. Lesions of the eye and contact-lens intolerance have also been associated with estrogen therapy. You may experience migraine headache, mild dizziness, depression, and increased sex drive (women) or decreased sex drive (men).