Abstract
Postmenopausal hormone replacement therapy (HRT) with estrogen plus progestogens is the first line therapy to treat menopausal symptoms. The progestogen is added to estrogen to reduce or eliminate the excess risk of endometrial cancer due to the unopposed effect of estrogen. Whereas progestin clearly opposes the proliferative and deleterious long-term actions of estrogen on the endometrium, the interference of progestin on the other estrogen action remains unclear. We previously reported that chronic subcutaneous 17α-estradiol (E2) in mice decreases platelet responsiveness, prolongs the tail-bleeding time and protects against acute thromboembolism. Here, we report the tissue-specific interference of progesterone (P4) on the action of E2 in ovariectomized mice. We first confirm that, in our experimental conditions, P4 attenuates the proliferative action of E2 on the uterus and the effects of E2 on vagina weight and lubrication. We then studied the effect of E2 combined with P4 on hemostasis and thrombosis in vivo in mice and found that P4 did not interfere with the main actions of E2 on platelets, bleeding time and arterial and venous thrombosis. Thus, whereas activation of progesterone receptor interferes with the action of E2 on its classic sex targets, P4 appears to have minimal effect on the hemostasis and thrombosis actions of E2, supporting the prominent role of estrogens and the accessory role of natural progestin on the extra-reproductive cells and tissues involved in thrombosis.
Highlights
Postmenopausal hormone replacement therapy (HRT) with estrogen alone or estrogen plus progestogens is the first line therapy to treat menopausal symptoms such as hot flushes, vaginal atrophy and insomnia
We explored the impact of a chronic treatment of E2 and P4 (E2+P4) on hemostasis and on thromboembolism and on carotid artery and inferior vena cava thrombosis in mouse
The addition of progestogens is required among postmenopausal women with an intact uterus in order to prevent the elevated risk of estrogen-induced endometrial hyperplasia and adenocarcinoma
Summary
Postmenopausal hormone replacement therapy (HRT) with estrogen alone or estrogen plus progestogens is the first line therapy to treat menopausal symptoms such as hot flushes, vaginal atrophy and insomnia. Effect of estradiol plus progesterone treatment on experimental thrombosis in mouse the corpus luteum during the luteal phase of the menstrual cycle and in the adrenal glands This hormone is involved in the function of female reproductive tissues, embryo implantation, maintenance of pregnancy and embryogenesis [1]. Progestogens produce their physiological and biological effects by interacting with intracellular progesterone receptors A (PR-A) and B (PR-B). The effects of progestogens are related to the interactions with PRs and with other steroid receptors such as androgen receptor, glucocorticoid receptor and mineralocorticoid receptor [3]
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