madman
Super Moderator
ABSTRACT
Background
The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control.
Purpose
To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women’s needs.
Results
All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation.
Conclusion
Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women’s needs and preferences.
SHORT CONDENSATION
For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women’s needs and desires.
The complex role of oestrogens in women’s health
Several types of oestrogens are produced by humans. The predominant oestrogen is E2, which is essential for the reproductive function and women’s wellbeing, followed by oestrone (E1) and oestriol (E3). A fourth type of oestrogen, estetrol (E4), is produced only during pregnancy by the foetal liver and placenta [9].
Oestrogens exert their tissue-specific biological effects through genomic mechanisms mediated by their interaction with nuclear oestrogen receptors (ERs) alpha (ERα) and beta (ERβ), as well as rapid non-genomic mechanisms through ERs localised at the plasma membrane [10]. These receptors have distinct tissue distribution. ERα are mainly expressed in the uterus, ovarian theca cells, Leydig cells in testes, breast, prostate stroma, epididymis, and liver [10,11]. ERα not only play a key role in reproduction, but exert important functions in many non-reproductive tissues [12].In contrast, ERβ are highly expressed in the bone marrow, brain, ovarian granulosa cells, prostate epithelium, and testes [10,11].
Beneficial effects of oestradiol
Oestrogens, particularly E2, contribute to the development and maintenance of secondary sexual characteristics, such as breast development and body fat distribution. Moreover,E2 plays a crucial role in regulating the vaginal mucosa function, influencing lubrication and elasticity. Besides, E2 has a stimulating effect on the uterus trophism, contributing to the endometrium growth [13].
In addition, specifically E2 exerts a widespread influence on the overall women’s health [14].
First, E2 has a protective effect on the cardiovascular system. It is involved in maintaining healthy blood vessels by promoting vasodilation and influencing blood pressure control [15]. E2 also leads to higher levels of high-densityl ipoprotein (HDL) and lower levels of low-density lipoprotein (LDL) cholesterol, respectively. This results in a general prevention of atheroma development and neointimal endothelial hyperplasia, with a reduced risk of cardiovascular disease during perimenopause [15,16]
Moreover, E2 entails a major role in bone health and metabolism, contributing to bone formation by stimulating osteoblast activity, and reducing bone resorption by inhibiting osteoclast activity. Therefore, E2 is vital for maintaining bone mineral density, thus preventing osteoporosis [17].
This hormone also plays an important role in mental health, potentially reducing the risk of neurodegenerative diseases [14]. Finally, E2 is involved in the immune response, with a close relationship between hormonal fluctuations during the menstrual cycle, immune cell activity and cytokine production [18].
The natural decline in ovarian E2 production during menopause leads to several metabolic changes, resulting in an increased risk of cardiovascular diseases, osteoporosis,and neurodegenerative diseases [14,19]
*Side effects and potential risks of natural and synthetic oestrogens
Characteristics of oestrogens in current combined oral contraceptives
Figure 1 and Table 1 provide an overview of chemical and pharmacokinetic characteristics of oestrogens currently used in COCs.
*Ethinylestradiol
*Natural oestrogens: 17β oestradiol and oestradiol valerate\
*Metabolism, haemostasis and cardiovascular risk
*Cycle control
*Estetrol
*The pharmacokinetic profile of estetrol
*The pharmacological profile of estetrol
Estetrol in oral contraception: the estetrol/drospirenone pill
*Metabolism, haemostasis and cardiovascular risk
*Cycle control
Selection of COC in clinical practice
Background
The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control.
Purpose
To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women’s needs.
Results
All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation.
Conclusion
Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women’s needs and preferences.
SHORT CONDENSATION
For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women’s needs and desires.
The complex role of oestrogens in women’s health
Several types of oestrogens are produced by humans. The predominant oestrogen is E2, which is essential for the reproductive function and women’s wellbeing, followed by oestrone (E1) and oestriol (E3). A fourth type of oestrogen, estetrol (E4), is produced only during pregnancy by the foetal liver and placenta [9].
Oestrogens exert their tissue-specific biological effects through genomic mechanisms mediated by their interaction with nuclear oestrogen receptors (ERs) alpha (ERα) and beta (ERβ), as well as rapid non-genomic mechanisms through ERs localised at the plasma membrane [10]. These receptors have distinct tissue distribution. ERα are mainly expressed in the uterus, ovarian theca cells, Leydig cells in testes, breast, prostate stroma, epididymis, and liver [10,11]. ERα not only play a key role in reproduction, but exert important functions in many non-reproductive tissues [12].In contrast, ERβ are highly expressed in the bone marrow, brain, ovarian granulosa cells, prostate epithelium, and testes [10,11].
Beneficial effects of oestradiol
Oestrogens, particularly E2, contribute to the development and maintenance of secondary sexual characteristics, such as breast development and body fat distribution. Moreover,E2 plays a crucial role in regulating the vaginal mucosa function, influencing lubrication and elasticity. Besides, E2 has a stimulating effect on the uterus trophism, contributing to the endometrium growth [13].
In addition, specifically E2 exerts a widespread influence on the overall women’s health [14].
First, E2 has a protective effect on the cardiovascular system. It is involved in maintaining healthy blood vessels by promoting vasodilation and influencing blood pressure control [15]. E2 also leads to higher levels of high-densityl ipoprotein (HDL) and lower levels of low-density lipoprotein (LDL) cholesterol, respectively. This results in a general prevention of atheroma development and neointimal endothelial hyperplasia, with a reduced risk of cardiovascular disease during perimenopause [15,16]
Moreover, E2 entails a major role in bone health and metabolism, contributing to bone formation by stimulating osteoblast activity, and reducing bone resorption by inhibiting osteoclast activity. Therefore, E2 is vital for maintaining bone mineral density, thus preventing osteoporosis [17].
This hormone also plays an important role in mental health, potentially reducing the risk of neurodegenerative diseases [14]. Finally, E2 is involved in the immune response, with a close relationship between hormonal fluctuations during the menstrual cycle, immune cell activity and cytokine production [18].
The natural decline in ovarian E2 production during menopause leads to several metabolic changes, resulting in an increased risk of cardiovascular diseases, osteoporosis,and neurodegenerative diseases [14,19]
*Side effects and potential risks of natural and synthetic oestrogens
Characteristics of oestrogens in current combined oral contraceptives
Figure 1 and Table 1 provide an overview of chemical and pharmacokinetic characteristics of oestrogens currently used in COCs.
*Ethinylestradiol
*Natural oestrogens: 17β oestradiol and oestradiol valerate\
*Metabolism, haemostasis and cardiovascular risk
*Cycle control
*Estetrol
*The pharmacokinetic profile of estetrol
*The pharmacological profile of estetrol
Estetrol in oral contraception: the estetrol/drospirenone pill
*Metabolism, haemostasis and cardiovascular risk
*Cycle control
Selection of COC in clinical practice
