Percutaneous estradiol/oral micronized progesterone has less-adverse effects and different gene regulations than oral conjugated equine estrogens/medroxyprogesterone acetate in the breasts of healthy women in vivo

Efficacy of Estradiol in Perimenopausal Depression: So Much Promise and So Few Answers

“…Several years following this publication, the results of the Women's Health Initiative (WHI), a study of the effects of HRT on almost 17,000 women, revealed an increase (rather than the expected decrease) in coronary heart disease, which, with the attendant increase in breast cancer, appeared to signal the end of menopausal hormone therapy . Subsequent studies, however, including reanalysis of the WHI data, revealed the following important contextual factors: (1) The results seen with ERT differed from those of HRT (e.g., no increased risk of coronary heart disease with ERT); (2) the hormones used in the WHI study (conjugated estrogens + medroxyprogesterone) were more likely to produce adverse effects on the cardiovasculature and breast than other hormone preparations; (3) the adverse effects seen in older women (who were far removed from the menopause) were not observed in perimenopausal women—i.e., the effects of ERT (or HRT) on perimenopausal women could not be inferred from those on postmenopausal women . (This last observation of the critical window or gap effect was predicted in earlier animal studies …”

“…Fourth, the type of hormone regimen may well affect the outcome observed. Biologic effects of conjugated estrogens differ from those of estradiol, and the presence of a progestin in combined HRT creates a different effects profile from that of estradiol when given as ERT . Additionally, the use of progestins either in tandem or in sequence with estrogen may cause mood destabilizing effects .…”

Evidence on the use of progesterone in menopausal hormone therapy

“…For the most part, in both studies, proliferation markers (mitotic index and proliferating cell nuclear antigen index) increased with E2 vs. placebo, decreased with P4 vs. placebo, and were comparable between E2/P4 and P4 or placebo 56,57 . In another study of postmenopausal women (n ¼ 77) taking two cycles of 0.625 mg CEE plus cyclic 5 mg MPA or 1.5 mg E2 gel plus cyclic oral 200 mg P4, breast cell proliferation significantly increased from baseline with CEE/MPA, but not with E2/P4 58,59 .…”

“…When mammographic breast density was evaluated in the PEPI trial, women randomized to CEE alone, CEE/cyclic MPA, CEE/continuous MPA, or CEE/cyclic P4 had 0.9%, 4.6%, 4.4%, and 3.1% increases in breast density, respectively, compared with placebo (À0.4%; p < 0.001 for combined progestogen group vs. placebo, with no difference among progestogen groups) 63 . A smaller Swedish study showed 18.9% of patients taking oral CEE 0.625 mg plus cyclic MPA 5 mg (n ¼ 37) had an increase in BI-RADS category of at least one level from baseline (p ¼ 0.01 vs. baseline) compared with 6.3% of women taking percutaneous E2 gel 1.5 mg plus oral P4 200 mg (n ¼ 32; p ¼ NS) 59 .…”

Chapitre 3 : Hormonothérapie ménopausique et cancer du sein

“…Les progestatifs sont actuellement cat egoris es en fonction de leur effet sur l'endom etre. En plus d'avoir exerc e une influence moindre sur la prolif eration des cellules canc ereuses mammaires dans le cadre d' etudes pr ecliniques 47 et sur la prolif eration de l' epith elium mammaire dans le cadre d'un essai randomis e de faible envergure men e chez des primates 48 , l'estradiol / progest erone par voie transdermique exerçait un effet moindre sur les marqueurs de la prolif eration cellulaire au sein de pr el evements de biopsie mammaire tir es de femmes postm enopaus ees normales 49…”