Progestogens and venous thromboembolism among postmenopausal women using hormone therapy

Abstract

Hormone therapy (HT) is the most effective treatment for correcting menopausal symptoms after menopause. HT initially consisted of estrogens alone and progestogens were secondly added to estrogens for preventing the risk of endometrial cancer associated to estrogens use. Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a major harmful effect of HT. It is now well known that oral and transdermal estrogens are differentially associated with VTE risk but progestogens may be another important determinant of the thrombotic risk among HT users. Both randomized controlled trials and metaanalysis of observational studies suggested that the VTE risk was higher among users of estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxyprogesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives were significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk. The effect of tibolone on VTE risk remains uncertain. In conclusion, progestogens may have differential effects on VTE risk according to the molecules and therefore represent an important potential determinant of the thrombotic risk among postmenopausal women using estrogens. Progestogens and VTE Finale version3/21

Progesterone for treatment of symptomatic menopausal women

“…A recent international clinical guideline recommended that progesterone be used in women with increased risk for thromboembolism 6 because it is without any signal of increased clot risk 47,71 .…”

Reprint of “Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe?”

“…In the Women's International Study of long Duration Estrogen after Menopause (WISDOM) trial, the results showed that users of CEE plus MPA had a higher thrombotic risk than those who used CEE alone; however, the difference in VTE risk did not reach statistical significance (HR = 2.39; 95%/CI: 0.62-9.24) [52]. In a study by Canonico et al [53], there was uncertainty regarding the impact of pregnane and 19-nortestosterone derivatives on VTE risk (OR = 1.3; 95% CI: 0.9-2.0 and OR = 1.4; 95% CI = 0.7-2.4, respectively), partly due to lack of statistical power for subgroup analysis.…”

South African Menopause Society revised consensus position statement on menopausal hormone therapy, 2014

“…[25] The route of delivery will impact on risk, with the highest risk being associated with oral EPT, followed by oral ET, and the lowest risk being associated with transdermal HT. [26,27] …”