Abstract
Progestogens (norethisterone acetate, medroxyprogesterone acetate, dydrogesterone,
micronized progesterone, levonorgestrel, drospirenone, and trimegestone) added to
estrogen for endometrial protection are reviewed. They can be given orally or vaginally,
norethisterone acetate can also be given transdermally, and levonorgestrel can be
given through the intrauterine route. Sequential use of progestogens protects the
endometrium if exposure lasts for at least 12 days/month; longer intervals are not
safe. Continuous use of progestogens, whether oral, transdermal, or intrauterine,
provides the most effective protection. Progestogen addition is accompanied with significant
elevations in breast cancer risk, the largest drawback of progestogen use, and dydrogesterone,
micronized progesterone, and a levonorgestrel intrauterine device may be safest in
this regard. Progestogens also double deep vein thrombosis risk and diminish the positive
effect of estrogen on colorectal cancer and vascular health. Recent data imply a neutral
effect of progestogens in combination with estrogen on Alzheimer's disease risk, but
the risk of vascular dementia is decreased. In conclusion, progestogens are a double-edged
sword, effectively protecting the endometrium but causing several side effects and
reducing many estrogen-induced benefits. With modern endometrial diagnostic tools,
the safety of low-dose unopposed estrogen regimens should be assessed in a prospective
controlled trial in women with an intact uterus.
Keywords
endometrium protection - androgen - breast cancer
