Preface

This edited volume is a collection of reviewed and relevant research chapters concerning the developments within the hormone therapy and replacement in cancer and aging-related diseases field of study. The book includes scholarly contributions by various authors and is edited by Drs. Leticia Rangel, Hephzibah Kirubamani, Ian Victor Silva, Paulo Cilas Morais Lyra Junior, Marcele Mattos De Souza, and Diandra Zipinotti Dos Santos.

Each contribution comes as a separate chapter complete in itself but directly related to the book's topics and objectives.

The book includes seven chapters, as follows: Thyroid Hormone Replacement Therapy in Patients with Various Types of Cancer; Bone Tumors: Types and Treatments; Role of Pineal Hormone Melatonin in a Woman's Life: From Conception to Decline of Life; Symptoms of Menopause; Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone; The Role of Hormone Replacement Therapy in the Treatment of Menopausal Symptoms in Patients Diagnosed with Gynecologic Cancer; Ovarian Hormonal Change-Related Energy Metabolism and Obesity in Menopausal Women.

The target audience comprises scholars and specialists in the field.

## **Leticia B. A. Rangel, Pharm. D., PhD.**

Full Professor and Investigator, Head of the Laboratory of Cellular and Molecular Biology of Human Cancer, Biotechnology Program/RENORBIO, Biochemistry and Pharmacology Program, Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Espirito Santo, Brazil

**1**

**Chapter 1**

**Abstract**

Types of Cancer

*and Shaker A. Mousa*

glioblastoma, renal cell carcinoma

tion of the state of actin [5, 6].

**1. Introduction**

Thyroid Hormone Replacement

Therapy in Patients with Various

*Aleck Hercbergs, Paul J. Davis, Hung-Yun Lin, Kelly A. Keating* 

Primary hypothyroidism is a common endocrine disorder that is effectively treated with l-thyroxine (T4) replacement. Preclinical and limited clinical evidence, however, indicates that T4 is a growth factor for a variety of cancers, acting at the thyroid hormone receptor on plasma membrane integrin αvβ3. T4 is the primary ligand for this receptor, whereas 3,5,3′-triiodo-l-thyronine (T3) is the principal intracellular thyroid hormone analogue. The evidence is reviewed here that T4 is a proliferative for breast, lung, kidney and prostate cancers and for glioblastoma, regulates cancer cell respiration and is a pro-angiogenic factor in established tumors. The recommendation is made that T3 be considered alternative replacement treat-

ment for patients with primary hypothyroidism who also have cancer.

**Keywords:** thyroid hormone receptors, integrin αvβ3, breast cancer, lung cancer,

Spontaneous primary hypothyroidism is a common disorder and prescriptions

for l-thyroxine (T4) replacement therapy are among the five most commonly prescribed drugs in the U.S. [1]. The predictable absorbance of T4 from the human gastrointestinal tract and its relatively long half-life in the circulation enable once daily replacement dosing and high patient compliance. 3,5,3′-triiodo-l-thyronine (T3) is also prescribed as thyroid hormone replacement, but its relatively short biologic half-life means that more than once daily dosing is required for replacement. Integrin αvβ3 is one of a family of plasma membrane proteins that are importantly involved in cell-to-cell and cell-extracellular matrix (ECM) protein interactions that are particularly relevant to tissue structure and function in cancer [2, 3]. αvβ3 is generously expressed by cancer cells and contains a receptor for thyroid hormone at which nongenomic actions of thyroid hormone are initiated [4, 5]. There are no structural homologies between the thyroid hormone receptor site on αvβ3 and the nuclear thyroid hormone receptors (TRs) at which genomic actions of the hormone are initiated [4, 5]. The large panel of genomic actions of T3 that are critical to the function of normal cells in species with thyroid glands involve TRs. T4 is a prohormone for T3 and is not important within cells, except perhaps for regula-
