WHAT ARE THEY?
Progesterone is naturally secreted by the ovary in
the second two weeks of the menstrual cycle in reproductive
age ovulating women. Progesterone or progesterone-like
substances called progestogens or progestin's are also
ingested by women in birth control pills, menopausal hormone
replacement therapy, or just sometimes to induce a menstrual
period or regulate abnormal bleeding problems if menses are
skipping or bleeding is irregular or prolonged. Progesterone
has been used also as therapy for PMS syndrome and for women
with infertility or frequent pregnancy loss.
Many magazine articles have
described the benefits and hazards of estrogens in women,
but progesterone effects are much less known. A recent
symposium, Fraser IS, Lobo R (eds and cochairs):Update
on progestogen therapy. J
Reprod Med 1999;44:139-232.
brought together much of the current knowledge about
progesterone administration for different purposes and helps
answer some questions that many women may be interested in.
ARE THEY GOOD FOR?
is the difference between progesterone and progestogens
Progesterone has the
identical chemical structure to the substance made in a
woman's body by the ovarian corpus luteum (gland formed
after an egg is
ovulated each month). Actually the
progesterone is now synthetically made but it behaves as
best we know, just like the body's natural progesterone once
it is absorbed into the blood stream. This is to be
distinguished from synthetic progesterone-like chemicals
called progestogens which bind to the body's progesterone
receptors and function for the most part, just like
progesterone. Because they are chemically different than
natural progesterone, they sometimes have side effects or
actions that are different than progesterone.
originally developed because they were capable of being
absorbed into the blood when ingested in pill form, whereas
was not orally absorbed. Recently,
however, it has been found that micronization
progesterone (making very tiny crystals of the progesterone)
enhances absorption from the gastrointestinal tract. Thus
micronized progesterone is now sometimes
being used for
menopausal hormone replacement therapy instead of progestogens. Birth control pills still have progestogens as
the active progesterone-like component.
have been used for years in infertility treatment and to
replace the natural progesterone in women with premature
ovarian failure. Progestogens are
used to treat abnormal
uterine bleeding and for contraception in birth control
and in Depo-ProveraÒ. They are also used to prevent
the negative effects of
estrogen on the uterus when used for
hormone replacement therapy and they are
used for the
treatment of PMS.
WHERE'S THE CONTROVERSY?
are two controversial topics you may have heard of. First is
the use of
natural versus synthetic Progestogens in hormone
Second is the use of progesterone in
the treatment of PMS, especially the recent popularity of
the NATURAL PROGESTERONE CREAMS.
replacement therapy (HRT) is recommended for most women
after menopause. HRT consists of the hormone estrogen and,
if your uterus has not been removed, progesterone. It's
commonly known that estrogen supplementation alone can cause
endometrial (uterine) cancer. When a Progestogens is added,
of uterine cancer is reduced below the base line
level. One of estrogen's many
benefits is it's ability to
reduce the risk of heart disease. One of the ways estrogen
does this is by increasing HDL or (good cholesterol).
Synthetic Progestogens tend to reduce this benefit. Natural
micronized progesterone does not appear to reduce estrogens
positive effect on cholesterol. Therefore this is one case
where the natural form of progesterone may be better for
(premenstrual syndrome) is a major problem for millions of
the world. Until recently there has been no
effective treatment. One of the theories about the causes of
PMS is that there is an imbalance between estrogen and
progesterone. This theory has led to the treatment of PMS
with progesterone. There have been over 20 scientific
studies of the treatment of PMS with progesterone, the vast
majority of which have found progesterone to be ineffective.
There are a few small studies that have shown some relief of
some symptoms of PMS with progesterone. Progesterone,
especially in EXPENSIVE cream form is marketed as a cure for
obesity, depression, foggy thinking, osteoporosis and
wrinkles to name a
few. These claims, made by some
manufactures are unsubstantiated.
In contrast to some of the
progestogens such as medroxyprogesterone acetate (Provera®,
Cycrin®) natural progesterone does not seem to suppress
What are the effects of too little or too much progesterone?
cholesterol (HDL), has no effect on blood pressure
or mood, and shows less of a tendency to cause increased
male-hormone-like effects such as facial hair growth.
synthetic progestogen may have a somewhat different
side-effect profile so it
is not easy to generalize.
to stabilize the tissue lining of the uterus (endometrium)
so if it is absent, such as with ovarian anovulation,
irregular and heavy menstrual bleeding
often occurs after a
period without any menstrual bleeding. Thus progesterone is
used to prevent this irregularity of bleeding if it is given
continuously. If, on the
other hand, a onetime bolus of
progesterone is given such as with a shot or with
days of oral pills, then the falling progesterone levels
will actually cause an estrogen-primed endometrium to slough
and therefore start a menses.
Too much progesterone often
causes tiredness and even sedation. This side effect
beneficial in a women who has epilepsy or even uterine
irritability causing preterm labor because progesterone in
high doses can decrease seizure activity and uterine
Progesterone tends to
promote vaginal dryness by counteracting the effect on
lubrication of estrogens and it can also decrease the amount
of menstruation or
block it entirely by reversing estrogen
effect on the growth of the uterine lining.
If a woman has
stopped having menses on a birth control pill, the progestogen component needs to be decreased if menstrual
bleeding is desirable.
Is it better to take progesterone as a pill, a shot,
a vaginal suppository or a cream?
All of the above forms of
progesterone and progestogens have been used.
The method of
administration is best determined by availability,
use and price. Absorption and duration of
action will vary by the form of
pills - peak
absorption is about 1-4 hours and is cleared by 24
hours. Taking the pills with food enhances absorption.
shots - usually given
in the form of progesterone in oil, doses peak at about
12 hours after administration and take at least 48 hours
or more to clear. There are depot forms of
medroxyprogesterone acetate (Depo-Provera®) that last at
least 12 weeks which gives it its contraceptive effect.
cream - absorbed to peak in 4 hours and cleared by 24
hours. Sometimes mixed in cocoa butter or propylene
glycol as the carrying agent. A cream is also
commercially available (Crinone®).
skin creams - creams
tend not to absorb through the skin very well but
alcohol-based gels are effective with a once a day
application. A 10% alcohol and propylene glycol base
also seems to be quite effective and clears by 24 hours.
How is progesterone
used to regulate abnormal bleeding?
There are two ways that
progesterone can be effective to regulate abnormal menses or
bleeding. If given continuously such as in birth control
pills or with postmenopausal hormone replacement therapy,
progesterone will prevent menstrual sloughing as long as
there is a small amount of estrogen present. If birth
control pills are taken continuously so that a woman skips
the week of the "placebo" or inactive pills and immediately
begins a new pill pack, then she will not have any menses at
all. This is the pill regimen used for endometriosis to
suppress endometrial growth and thus inactivate
endometriosis. If progesterone doses are too small without
any estrogen around, such as with the "mini" birth control
pill, breakthrough bleeding often occurs because estrogen is
needed to stabilize the blood vessels in the base layer of
the endometrium. Such bleeding would be called
atrophic bleeding since the tissue is very bare down
to its basal layer.
The second way
in which progesterone is used to control abnormal menstrual
bleeding is to induce a menses by giving a bolus of
progesterone and then discontinuing it. This could be by a
shot of progesterone in oil or by taking 5-10 days of
progesterone or progestogen by pill. The rule-of-thumb has
been that if a woman is not pregnant and estrogen had
previously stimulated even a small amount of endometrial
growth, then a menstrual-like bleed would result within
about 10 days of stopping the progesterone. Unfortunately,
this regimen only works 70-95% of the time with the shots
being less effective and the progestogens (Provera®,
dydrogesterone) being 90-95% successful. Common doses used
to induce withdrawal bleeding would be:
acetate (Provera®) 5 mg twice a day or 10 mg once a day
for 5 days
progesterone 200 - 300 mg for 10 days
progesterone in oil
shots intramuscularly, 100-200 mg for one dose
pills (most monophasic pills with all the same dose of
estrogen and progestogen), one pill each day for 4-5
days (for example using pills out of a pill pack or
using the emergency contraceptive regimen but taking one
pill each day for 4 days instead of all at once.
Sometimes if the bleeding has
been quite heavy or prolonged, the progestogens will be
given longer than 5-10 days just to allow a woman's recovery
from the constant bleeding and blood loss.
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:
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®
density lipoproteins - all of the hormone regimen
combinations lowered the bad cholesterol (LDL)
pressure - there were no effects of estrogen alone or
any of the combinations with progestogens or
progesterone on either systolic or diastolic blood
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.
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.
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.
Progestogens should not be used if you
have had blood clots in the legs (thrombophlebitis) or liver
disease. Use in pregnancy requires careful physician
surveillance. Progesterone can also cause bloating, breast
tenderness, weight gain, headache, moodiness and irregular
vaginal bleeding. Progestogens can cause some medical
conditions to worsen examples are asthma, heart failure,
epilepsy and migraine headache. Natural progesterone tends
to have fewer side effects.
Yams produce a compound that is used by the pharmaceutical
industry to produce progestogens. The human body can NOT do
this. Many PMS and menopausal remedies contain wild yam or
Mexican yam extract. Often claims are made that this product
is in fact progesterone, it is not. Dioscorea may have
beneficial effects and it may be useful for some conditions,
but it is not the same as progesterone.
Looking For The
Type of Progesterone
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