In postmenopausal women, partly in relation to advancing age and partl
y due to oestrogen deficiency, there is a frequent increase in body we
ight, and more specifically, in android fat distribution. In addition,
loss of ovarian function is associated with the development of a more
atherogenic profile with increased triglycerides, LDL-cholesterol and
its smaller dense subfractions, decreased HDL- and HDL2-cholesterol a
nd, potentially, an irregular increase in Lp(a). Not only does oestrog
en therapy counteract all these changes towards a definitely less athe
rogenic profile but oestrogens seem also implicated in reducing LDL ox
idative products, in favouring a higher ratio of prostacyclin to throm
boxane and, potentially, of endothelium derived relaxing factor to end
othelin, and also in acting as a calcium antagonist in the vessel wall
. All of these favourable vascular effects are not solely attributable
to lipid-related oestrogen effects. Excess weight and central obesity
, diet changes and lack of exercise, more frequent with advancing age,
all concur to alter glucose tolerance and increase insulin resistance
during the postmenopause. Impaired glucose tolerance and diabetes mel
litus may be found in nearly 20% of women aged 55 to 65 years. In addi
tion, oestrogen deficiency may be further responsible for decreased pa
ncreatic insulin secretion and alteration of its metabolic clearance r
ate-changes that can be reversed toward improved insulin secretion and
sensitivity by oestrogen treatment in small dosages. By contrast, syn
thetic androgenic progestins can counteract these effects of oestrogen
s more than progesterone derivatives do, and they may partly help to p
romote insulin resistance and hyperinsulinism. Indeed, long lasting hy
perinsulinaemia has been linked to an increased risk of cardiovascular
morbidity and mortality, maybe in relation to the effects of excess i
nsulin on vascular wall and its adverse impact on lipoprotein metaboli
sm and haemostatic factors. Accordingly, long term administration of a
ndrogenic progestins at the menopause should be best avoided.