Does progesterone block or lessen the beneficial effect of estrogen on heart disease and osteoporosis prevention?

The effect of various estrogen and progestogen/progesterone combinations have been looked at extensively in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, Writing Group for the PEPI Trial: Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1995;273:199-208.  

Some of the following generalizations can be drawn:

• high density lipoproteins - basically progestogens such as Provera® lessen some of the estrogen effect of raising HDL (good cholesterol) but in combination with estrogen, the net effect is still to raise HDL a small amount. Natural progesterone does not blunt this response and when used with estrogen, HDLs rise more than when Prover® is used.
• low density lipoproteins - all of the hormone regimen combinations lowered the bad cholesterol (LDL)
• blood pressure - there were no effects of estrogen alone or any of the combinations with progestogens or progesterone on either systolic or diastolic blood pressure.
• weight and abdominal girth - interestingly, all women, even those who had no estrogen or progesterone, gained weight and increased abdominal girth during this menopausal study. The women who took any hormonal therapy gained LESS weight and had LESS increase in abdominal girth.
• Blood sugar - all hormonal regimens resulted in a lower fasting blood sugar. However,the estrogen with medroxyprogesterone acetate (Provera®) raised the 2-hour post glucose blood sugar implying that the progestogen may worsen a diabetic tendency.

Does progesterone cause mood changes?

The brain has both estrogen and progesterone receptors. In women who have epilepsy, seizures are known to occur more frequently during times of high estrogen (late follicular phase and ovulation) and they are decreased when progesterone is high.

In this sense, progesterone acts a a brain anesthetic to some degree. High doses of progesterone can be very sedating.

Women who have depression have lower brain levels of serotonin, thus the success of medications that block the body's degradation of serotonin and allow brain levels to remain higher.

Estrogens are known to block one of the enzymes (monoamine oxidase - MAO) which degrades serotonin with the result of elevating mood. Progestogens, probably more so than natural progesterone, increase MAO concentration thus producing depression and irritability.

Pure progestogen treatment without estrogen, such as DepoProvera® is know to worsen depression in women who already have a tendency toward or clinical signs of depression.

The combination of estrogen plus progestogens such as used in birth control pills and menopausal hormonal replacement therapy does not tend to worsen mood because the compounds are neutralizing each other.

There are some women who are more sensitive to certain hormones so their doses may need to be adjusted.

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