Tissue-selective estrogen regulation capabilities in postmenopausal women

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Abstract

Postmenopause is a physiological period in a woman’s life characterized by a decrease in levels of sex steroid hormones. Estrogen deficiency is associated with the development of vasomotor symptoms, genitourinary syndrome of menopause (GSM), skin and breast tissue changes, lipid and carbohydrate disorders, endothelial dysfunction, and increased cardiometabolic risks, as well as decreased bone mineral density. To date, the most effective method for correcting various symptoms of menopause is menopausal hormone therapy; one of its options that can be used in postmenopause is considered to be tibolone, a tissue–selective regulator of estrogenic activity.

The review presents the history of studying the molecule of tibolone, which is a synthetic steroid with estrogenic, progestogenic, and androgenic activity. The mechanism of action of tibolone involves the formation of three active metabolites: 3-β-hydroxytibolone and 3-α-hydroxytibolone, which are responsible for estrogenic effects of tibolone and mainly present in an inactive sulfated form, and Δ4-tibolone, which has progestogenic and androgenic activity. Tibolone use in postmenopausal women has demonstrated effective alleviation of vasomotor symptoms, GSM, increase in bone mineral density, and positive effects on the cardiovascular and central nervous systems; stimulating effect on the endometrium was absent. There is also a discussion of mechanism of tibolone impact on breast tissue. Thus, tibolone exhibits selective estrogenic activity and regulates actions in different tissues, making it a unique representative of the STEAR class.

Conclusion: Tibolone is the first representative of tissue selective regulators of estrogenic activity. The diverse hormonal effects of tibolone are due to the action of several key metabolites on various tissues. Tibolone can currently be considered as an effective therapy for many postmenopausal women. It is necessary to take into account a number of characteristics of tibolone action and determine the possibility of prescribing the therapy for a specific patient on the basis of this information.

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About the authors

Maria I. Yarmolinskaya

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology; I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: m.yarmolinskaya@gmail.com
SPIN-code: 3686-3605
Scopus Author ID: 7801562649
ResearcherId: P-2183-2014

Dr. Med. Sci., Professor of the Russian Academy of Sciences, Head of the Department of Gynecology and Endocrinology, Head of the Center of Diagnostics and Treatment of Endometriosis, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Professor, Department of Obstetrics and Gynecology, I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia

Russian Federation, St. Petersburg; St. Petersburg

Anastasiya V. Koloshkina

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Email: nastyasalukhova@gmail.com
ORCID iD: 0000-0002-5200-7672

Resident

Russian Federation, St. Petersburg

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2. Fig. 1. Relative concentrations of tibolone metabolites in different tissues (adapted from [16])

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3. Fig. 2. Possible mechanisms of modulation of tissue selectivity of tibolone in mammary gland and endometrium (adapted from [18])

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4. Fig 3. Effect of tibolone on estrogen metabolism in breast tissue (adapted from [41])

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