Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary?

Abstract

Background: Throughout history, menopause has been regarded as a transition in a woman’s life. With the increase in life expectancy, women now spend more than a third of their lives in menopause. During these years, women may experience intolerable symptoms both physically and mentally, leading them to seek clinical advice. It is imperative for healthcare providers to improve the quality of life by reducing bothersome menopausal symptoms and preventing disorders such as osteoporosis and atherosclerosis. The current treatment in the form of hormone replacement therapy (HRT) is sometimes inadequate with several limitations and adverse effects. Objective and rationale: The current review aims to discuss the need, efficacy, and limitations of current HRT; the role of other ovarian hormones, and where we stand in comparison with ovary-in situ; and finally, explore towards the preparation of an HRT model by regeneration of ovaries tissues through stem cells which can replicate a functional ovary. Search methods: Four electronic databases (MEDLINE, Embase, Web of Science and CINAHL) were searched from database inception until 26 April 2018, using a combination of relevant controlled vocabulary terms and free-text terms related to ‘menopause’, ‘hormone replacement therapy’, ‘ovary regeneration’, ‘stem cells’ and ‘ovarian transplantation’. Outcomes: We present a synthesis of the existing data on the efficacy and limitations of HRT. HRT is far from adequate in postmenopausal women with symptoms of hormone deprivation as it fails to deliver all hormones secreted by naïve ovarian tissue. Moreover, the pharmacokinetics of synthetic hormones makes them substantially different from natural ones. Not only does the number and type of hormones given in HRT matter, but the route of delivering and their release in circulation are also imperative. The hormones are delivered either orally or topically in a non-physiological uniform manner, which brings along with it several side effects. These identify the need for a hormone delivery system which replicates, integrates and reacts as per the requirement of the female body. Wider implications: The review outlines the strengths and weaknesses of HRT and highlights the potential areas for future research. There is a tremendous potential for research in this field to understand the collective roles of the various ovarian hormones and to devise an auto-regulated hormone delivery system which replicates the normal physiology. Its clinical applications can prove to be transformative for postmenopausal women helping them to lead a healthy and productive life.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions

“…The follicle functions are regulated by the feedback mechanism of the hypothalamic-pituitary-ovarian (HPO) axis. The systemic hormone therapy skips this feedback mechanism and, therefore, has limitations in controlling the therapeutic hormone levels with the aforementioned side effects ( 10 ). Artificial follicles engineered with cultures of autologous cells in an organ model system are a promising solution to address the side effects associated with the standard hormone therapy ( 11 ).…”

Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone

“…Endometrial safety is a grill for challenge menopausal and postmenopausal HTs, because the bleeding and the risks of hyperplasia and cancer are discussed in the 70 years of MHT history, years with many waves of increased and decreased enthusiasm on the benefits and risks of MTH. The aim of replacement and restoration of ovarian functions in postmenopausal women with estrogens and progesterone is only a modest attempt for women's health, because there are missing other molecules as testosterone, activin, inhibin, anti-Müllerian hormone (AMH) and insulin-like growth factor 1 (IGF-1), and many other connected to these, which have an immense significance on a woman's physiology, and all of them may influence endometrial actions of MHT [84].…”

Tamoxifen protective role in ovariectomy related- metabolic disorders in rats

“…Nevertheless, a minority of postmenopausal women currently take E2 or HRT for long period to reveal its maximum benefits, because of its side effects such as vaginal bleeding and breast pain and uterine, breast cancer risks (20). In addition, it is also known that inflammation is a secondary to impaired oxidative metabolism.…”