Progestogen safety and tolerance in hormonal replacement therapy

Abstract

Today, it is a mandatory practice to prescribe a combination of estrogens and progestogens for menopausal women requiring hormone therapy and with a uterus. The WHI study and its reanalysis demonstrate a big difference in results between the conjugated equin estrogen (CEE) only vs.CEE plus medroxyprogesterone acetate (MPA) arms in relation with breast cancer and cardiovascular risk. The conclusion is that risk is clearly higher in the arm with MPA than in the CEE only arm. Although the only progestogen used in the WHI study was medroxyprogesterone acetate, side effects and intolerance have been extrapolated as a class effect to all progestogens. Areas covered: Progestogen tolerance and side effects in hormone therapy were reviewed. For that purpose, a limited literature search was conducted on key resources including Pubmed, the Cochrane Library, ECRI, and major international health technology agencies. Expert opinion: Many of the tolerance effects are based on limited data. There are no double-blind randomized trials comparing long-term safety for breast cancer and cardiovascular risk among different progestogens. Short-term clinical studies, observational, and in animal and in vitro studies indicate that both micronized progesterone and dydrogesterone are the safer progestogens with an acceptable metabolic profile.

Hormone Replacement Therapy in a Patient with Hypogonadism and Coexisting Medical Conditions

“…Taking into consideration the existing medical conditions and the increased risk of VTE in our patient, it was decided to initiate transdermal estrogen treatment with cyclic oral dydrogesterone. Again, there is little evidence concerning endometrial protection in adolescents and young adults, but dydrogesterone appears to be a safe progestogen with an acceptable metabolic profile, similar to micronized progesterone (22).…”

Hormone therapy for first-line management of menopausal symptoms: Practical recommendations

“…8–12 The dose and duration of progestogen per cycle depends on the type and dose of oestrogen being administered, and should be aligned with the endometrial effectiveness of the progestogen as assessed in clinical studies involving endometrial biopsies. 25 The metabolic and tolerability profiles of available progestogens should also be considered, as well as patient-specific factors including potential risk factors for HT.…”

Thrombosis and Gestagens

“…В частности, гестагены III-IV поколения (III -гестоден, дезогестрел, норгестимат, IV (новые) -дросперинон) оказались более тромбогенными по сравнению с препаратами ранних поколений (левоноргестрел) [29]. В то же время сам прогестерон и его производное дидрогестерон, как выяснилось, наиболее безопасны в отношении тромботического риска [30]. Очевидные различия эффектов гестагенных компонентов ГП на гемостаз могут объясняться дополнительными активностями стероидов -влиянием на андрогенные, минералокортикоидные и глюкокортикоидные рецепторы.…”

“…К этим препаратам относят сам прогестерон (микронизированную лекарственную форму) и дидрогестерон, которые оказались наиболее безопасными в отношении тромботического риска. В 2016 году в Великобритании опубликованы данные о том, что использование эстрадиола/дидрогестерона (месяцы -годы) у пациенток менопаузального возраста не повышает риск инфаркта миокарда, ишемического инсульта и ВТЭ по сравнению с другими типами МГТ [30]. Последние публикации, анализирующие безопасность ГП, свидетельствуют о том, что не увеличивает риск тромботических осложнений комбинация эстрадиола с дидрогестероном [16].…”