Very few studies were available of the risks for colorectal cancer, cutaneous malignant melanoma or thyroid cancer that allowed a distinction between use of post-menopausal oestrogen progestogen and oestrogen therapy. They do not suggest an increased risk, but all included few exposed subjects. Only one study was available on combined oestrogen and progestogen therapy, in which conjugated equine oestrogens were tested with medroxyprogesterone acetate. The proportion of absorbed hormones that becomes biologically available depends on the extent of enterohepatic circulation and metabolic transformation of pro-drugs. Oestrogens and progestogens may affect each other s disposition.
Many progestogens have oestrogenic activity and can modify the effects of oestrogens.
The addition of progestogens to therapy may decrease cell proliferation in human endometrium over that with oestrogen alone. The extent of the cell proliferation response depends on the doses of oestrogen and progestogen, increasing with higher doses of oestrogen and decreasing with more progestogen, as compared with oestrogen alone. In ovariectomized cynomolgus monkeys, the conjugated oestrogen progestogen combination caused a higher incidence of mammary gland hyperplasia than did conjugated equine oestrogens alone. No information was available on whether the effect of oestrogen progestogen combinations on the mammary gland is modified by sequential exposure to progestogens, by body weight or by the recency or duration of exposure in experimental animals. Similarly, no information was available on the possible relationship between exposure to oestrogen progestogen combinations and the degree of malignancy of breast tumours.