Bispecific Antibodies Are Associated With Progressive Multifocal Leukoencephalopathy.

Unopposed estrogen is a physiological state in which estrogen levels are elevated or sustained without adequate progesterone [, ]. Progesterone normally counterbalances the proliferative effects of estrogen in estrogen-responsive tissues, such as the endometrium and breast epithelium []. In the event of this balance being upset, as in clinical situations such as anovulatory cycles, perimenopause, polycyclic ovary syndrome (PCOS) or with estrogen only hormone replacement therapy (HRT), estrogen effects continue without any check []. This chronic stimulation leads to hyperproliferation that can lead to genomic instability, chronic inflammation and progress to malignant transformation. Unopposed estrogen has been strongly associated with carcinogenesis in several hormone-sensitive cancers []. Harmless estrogen (unopposed) has been most consistently associated with endometrial hyperplasia and type I endometrioid endometrial carcinoma, especially in conditions like chronic anovulation, obesity and estrogen-only menopausal hormone therapy []. Likewise, too much estrogen in breast tissue can cause the mammary epithelial cells to start multiplying and multiplying cells can be more susceptible to changes and development into estrogen receptor-positive breast cancer tissue []. An increasing body of evidence also reflects a possible relationship between long-term estrogen exposure and the development of ovarian cancer particularly in post-menopausal women [, ]. In contrast, link between the estrogen level and ovarian cancer is less certain. Evidence from large, epidemiologic, and meta-analytic studies indicate a moderate elevation in risk for Ovarian Cancer may exist with women taking Menopausal Hormone Therapy (MHT), but studies are heterogeneous and risk depends on the types of tumors, length of exposure, and the type of hormone therapy [, ]. Hence, a discussion of ovarian cancer as a possible estrogen related cancer, and not as a direct or proven outcome of unopposed estrogen is appropriate [–]. These observations highlight the need for improved monitoring of estrogen dominance to support early detection and hormone-based intervention. Although of clinical significance, unopposed estrogen is a difficult condition to diagnose and follow precisely. The traditional methods of hormone measurement, such as immunoassays and ELISAs, provide only static measurements of serum estrogen and progesterone levels and do not capture dynamic hormonal activity or real-time fluctuations [, ]. Furthermore, such methods do not accurately reflect local activity of hormones or slight changes in hormones at an early stage []. Available screening tools for traditional cancer (mammography, pelvic ultrasound, endometrial biopsy) are usually applied when a person is already diseased or when one is already at high-risk, and therefore are not effective in preventing cancer [–]. Consequently, a number of instances of hormone-dependent cancer are detected at later stages of development when they are harder to cure.