I decided to see
whether I couldn't get some sense of the difficult
progesterone question. Do we need it? What is it good
for? It's an enormous and complicated topic, but, as
usual, the direct concerns of women in surgical menopause
have been given less attention, but for those of us in
surgical menopause it may be essential to feeling good.
It's such a big topic, I have to feel that this is a
preliminary report from the trenches of the medical
journals--but here goes.....
Progesterone is a
hormone, which means that it's a messenger chemical that
moves through the bloodstream, across a cell's membrane,
and attaches to receptors in a cell's nucleus. Hormones
are like keys searching for their locks. When they find
the lock that they fit, they insert themselves and open
the lock, starting one of many processes. Cells with
these progesterone receptors are in the uterus, the
central nervous system, the mammary glands in the breast,
and the pituitary gland--as well as urinary and vaginal
tissues.(9) It's most important role for the survival of
the species is the fact it maintains pregnancy. Another
word for pregnancy is gestation--pro-gestation =
pro-gesterone. Progesterone levels are controlled by
luteinizing hormone, which starts the chain of events
that takes cholesterol and converts it pregnenolone,
which in turn becomes progesterone. The end of
progesterone release each month premenopause is the
signal for menstruation.(9)
progesterone can be made, not only in the ovary, but also
in the adrenal glands and glial cells in the central
nervous system (not to mention the placenta and even the
testes, for thems as got 'em) (9). Some think that up to
60% of progesterone in healthy premenopausal women is
made in the adrenal glands, (35) so many in surgical
menopause may not need replacement once our adrenal
glands get healthy.
The trouble comes in
the Hormone Jungle (though of course it can strike
others). We take extra estrogen and the ratio of
progesterone to estrogen goes out of whack. As Dr. Joseph
Collins says, "estrogen dominance" is the wrong term.
It's progesterone too low in relation to estrogen that
causes the problems--from the serious to just the
unpleasant--though the estrogen itself may be low,
progesterone is even lower (which is one reason why the
too high/too low charts can be confusing). According to
Collins, the normal premenopause ratio is somewhere
between 20/1 and 120/1, Progesterone/Estrogen.
When the balance tips
toward estrogen, it can contribute toward impaired liver
function, it can decrease the action of vitamin B6, and
it can increase aldosterone and prolactin.(16) Of course,
it's not good if the progesterone levels get way too high
in relation to estrogen either; then insulin resistance
gets worse, depression and fatigue get worse, and libido
But many of us already
know all about progesterone/estrogen ratios when they go
out of whack. That's what a lot of PMS is. Five to 10
days before menstruation, the ratio shifts so that
estrogen goes up and progesterone goes down. We get
irritable and aggressive because the estrogen boosts
norepinephrine in the brain, and we retain salt and water
because lower progesterone causes higher aldosterone.
Emotional stress and high norepinephrine make
progesterone levels even lower, and you can see why some
women have it so hard. (3)
Just to remind
ourselves, the symptoms of PMS are abdominal distension,
breast tenderness, headaches, fatigue, dizziness, weight
gain, fluid retention, joint pain, pelvic congestion,
changes in appetite, poor immunity, diarrhea,
constipation, herpes outbreaks, acne, insomnia, poor
memory, grief, irritability, anger, anxiety, poor
concentration, and confusion (3), not to mention edema
(swelling) of the fingers and ankles (16) Estrogen is up
and progesterone is down (17, 18, 19) and this list reads
like a lot of the thickets and bramble patches in the
Hormone Jungle. When the ratio is off, hypothyroid and
elevated prolactin (breast soreness and even discharge
from nipples) are common, and aldosterone goes up.(16)
What are the conditions
that progesterone can help?
Allergies are often
worse with low progesterone.(35)
One of the most common
tiger traps in the Hormone Jungle is the horrible anxiety
that can come when the ratio is out of balance. Anxiety,
nervousness, mood swings, and nervous tension and signs
that estrogen is high and progesterone is low.(3) One way
to address it is to increase levels of progesterone. But
there are some natural ways to help your body do that.
Vitamin B6 and magnesium (estrogen creates deficiencies)
actually help with progesterone levels. Also known to
help a lot is to increase fiber in your diet and to
decrease saturated fat and refined carbohydrates (now
where have we heard that before).(3) Progesterone itself
soothes the nervous system. Progesterone can become
chemicals in the brain that act just like Xanax and
Valium to calm anxiety--though of course it's the other
way around. Xanax and Valium act like progesterone!(35)
Another pathway that affects mood is that high estrogen
to progesterone ratios lower endorphins,(18) and
endorphins normalize or improve mood.(16)
While the studies of
progesterone alone don't show a real benefit, studies of
estrogen in combination with bio-identical progesterone
show an increase in building bone beyond estrogen's
effect alone. So here's a clear case where estrogen and
progesterone in balance enhance each other.(35) A test of
mice showed that progesterone decreases bone turnover.
Less bone was lost in the spine and in the femur when
they were given progesterone, the higher in this case the
Progesterone can help
clear the brain fog. Dr. Collins thinks that one of the
signs of progesterone dropping too low is in fact a sense
of confusion.(35) One preliminary study showed that
postmenopausal women did better on some brain tests when
they were on estrogen plus either progestin or
progesterone than on estrogen alone.(4) Spatial cognition
tests too showed that estrogen alone didn't have a
positive effect. Though in this case, testosterone showed
the most benefit.(28) Even more interesting, was that
brain-damaged rats left in a water maze (aren't you glad
you're not a lab rat?) did much better when given
estradiol plus progesterone. They learned the maze and
wandered less. Progesterone seems to protect learning and
memory.(14) In another rat study, they mimicked the
damage done by a stroke on the brain. Rats given
progesterone after the stroke had significantly less
damage and had more improvement in function afterward. In
that case, progesterone protects the brain and nerves and
may even help them regenerate.(13, 21) Progesterone can
reduce cerebral edema (21) after an injury too.
influence extends to epilepsy too. It's anti-seizure
effect is well known.(10) The problem is though that the
metabolites play a big role, so that creams and the
transvaginal may not have this good effect.
Progesterone can be
sedating, bringing sleep on.(35) It also balances
estrogen's effect on serotonin and norepinephrine, which
both act to "overcaffeinate" us--causing us to be wired.
It also helps too improve breathing patterns, even making
sleep apnea better in some.(35). It's important to
remember though that it's bio-identical progesterone that
makes the biggest difference. There was a study that
compared women on either Premarin and Provera (synthetic
progestin) or Premarin and Prometrium (bio-identical
progesterone). Women taking the Prometrium found they
fell asleep more easily and stayed asleep for more of the
night.(26) On the other hand, too much progesterone can
be sedating and create fatigue, so you can have too much
of a good thing. (35)
The picture isn't as
clear here, but one beneficial effect may be the decrease
in water retention. Some studies seem to show that the
primary directly hormonal trigger of migraines is the
withdrawal of estrogen. It's the changes in the sustained
estrogen levels that appeared to trigger headaches the
most often, including drops in progesterone levels.(29)
Just our experience in the Jungle has shown that
progesterone often helps with migraines that appear after
One of the signs that
the progesterone estrogen ratio is out of balance is
pain--muscle pains and joint inflammation.(35)
Progesterone metabolites (the chemicals it breaks down
into) are like barbiturates (well, barbiturates are like
progesterone--which comes first the chicken or the egg
after all?). They enter gamma aminobutyric acid receptors
in the central nervous system and turn off the pain.(9)
Inflammatory hyperalgesia is soothed by progesterone,
which plugs into receptors in the spinal cord and brings
Though a lot of studies
need to be done, there's a steady drumbeat now of
preliminary studies pointing to hormone replacement as an
immediate treatment for urinary tract problems. They've
been excited to find that there are both estrogen and
progesterone receptors in both the urinary tract and the
vagina. As one guy said, these seem to be target organs
for estrogen and progesterone.(32) They have a more
indirect effect too that makes them excited. After
menopause, the pelvic floor gets weaker, leading to
prolapse and incontinence. The muscle that controls the
pelvic floor has its own estrogen and progesterone
receptors. The connective tissues do too. So once again,
having both estrogen and progesterone seems
Weight gain, bloating,
discomfort, breast tenderness, swelling of hands and
ankles are all signs of high levels of aldosterone, which
are caused by excess estrogen, magnesium deficiencies,
and stress knocking out the good ratio.(16)
By balancing estrogen,
does progesterone hurt some of estrogen's
One reason that doctors
can be adamant that women without uteruses should not be
taking progesterone/progestins is that early studies
using estrogen plus progestin showed that progestins
decreased or even eliminated estrogen's good effects.
However, now that more studies are being made with
bio-identical progesterone, the picture is changing. The
PEPI studies (you can find more on these in the heart
articles here on the HJ) showed that bio-identical
progesterone did not lower estrogen's benefit at all.
There have been some recent studies that have shown it
may even enhance estrogen's benefits when in balance with
it. The abnormal growth of cardiac fibroblasts is
connected to high blood pressure and heart attack.
Estrogen alone did not slow the growth of fibroblasts but
estradiol plus progesterone did.(24) Also a study of
plaque in the arteries showed that, though estriol, low
progesterone, and high progesterone all improved the
plaque, it was progesterone that had the most effect.(27)
It's been known to decrease high blood pressure.(35)
It's just possible that
progesterone might make hot flashes a bit worse,
especially at first. It increases blood flow to the skin,
increases the temperature of the skin, and increases
metabolism, so you can sweat more.(35) It's not really a
hot flash, but it does raise your thermostat.
This is delicate
balance in the Jungle. If the ratio is right, libido is
improved and so it vaginal health. If progesterone is too
high, then libido is decreased as depression is
increased.(35) It can activate dopamine, and if the ratio
is right, increase the pleasure from sex.(22) So the
trick is getting the balance right.
The subject of weight
in the Hormone Jungle is vexed. Estrogen clearly has
benefits for the digestive tract and insulin levels and
fat distribution, but when it's high, it also creates
water retention and weight gain, sometimes of many
pounds.(33) Progesterone in balance can release the water
weight. Estrogen can also cause a craving for sweets and
carbs, which progesterone alone might not eliminate.(23)
While some researchers feel that progesterone alone has
no effect on body weight either way,(25) progesterone can
upset estrogen's good effects on insulin. It may also,
especially when progesterone is too high, stimulate the
appetite.(35) After all, a pregnant woman is supposed to
eat more. It's interesting that one way progesterone
makes us feel better is through dopamine. And dopamine is
the brain chemical that rewards us. In rats, they found
that progesterone released more dopamine (feel good
chemical), and a shot of estrogen changed it so the rats
felt that food was a huge reward (more than sex even).(7,
8) So, getting the right balance is clearly necessary!
What are the kinds of
Prometrium is the brand
name of oral bio-identical progesterone that's
micronized. "Micronized" means progesterone is reduced to
particle sizes smaller than 10 micrometers (that's tiny).
It allows it to pass through the intestinal wall.
Suspension in oil and in gelatin capsules helps it absorb
more.(9) It seems to produce quite variable amounts in
women because it goes through the liver first.
Progesterone levels peak within 2 to 3 hours of taking it
and remain high for up to 12 hours. They return to
baseline 24 hours after taken.(9) Over time, levels are
more sustained and can take 84 hours to baseline.(9) This
might be a clue if Prometrium starts to have side effects
over time. The dose might be too high. Taking it with
food resulted in increased peak levels.(9) In terms of
benefits, it's like taking estrogen alone, and it makes
no changes in liver enzyme levels (that's good) (9)
Because it's oral, it goes through the liver first, where
90% of it is crunched up into other chemicals. As a
result, these discard chemicals form unnaturally high
levels in the blood stream. This is why Prometrium can
cause dizziness and drowsiness, even if the ratio with
estrogen may be ok.(1) It's still far better than the
synthetic progestins--more health benefits and clear
improvement in mood for the majority.(4) Some studies
have shown that Prometrium has a much better effect on
menopausal symptoms all around than the progestins.(6)
Another form of
micronized bio-identical progesterone comes in skin
creams (if chemicals aren't made teeny tiny, they don't
pass through the skin barrier). This is very
controversial. Scientific studies can't get a consistent
handle on how much progesterone is getting through. The
skin barrier doesn't seem to allow for the administration
of progesterone in the quantities necessary to protect
against uterine cancer if one still has a uterus and one
is taking estrogen.(1) It seems pretty clear, even in
double-blind studies, that 1/4 tsp containing 20 mg of
progesterone to the skin daily will improve menopausal
symptoms by 83%--definitely better than a placebo. But
they can't find a consistent gain in bone density (15) It
seems as though the creams start to raise progesterone
levels in about 60 minutes and reach peak levels at 1 to
4 hours after applying. Oral and vaginal progesterone
reaches far higher doses, but a cream, especially a
compounded cream with more strength and consistent
amounts, can be enough to balance the
progesterone/estrogen ratio. It does not seem to be
strong enough to control the endometrium, which has
consequences for sisters with endometriosis.(20) No one
has figured out how it works, since it doesn't enter the
bloodstream directly. Dr. Lee's theories haven't held up
and they haven't found an alternative yet.
progesterone is a practical nonoral route that delivers
high levels of progesterone direct to the uterus or the
pelvic area. This might be a good choice for
endometriosis control if other forms of progesterone
throw off the balance. It has fewer side effects than
other means.(1) Blood levels stay on a plateau, being
much steadier. It probably doesn't help with anxiety and
the other brain chemicals but it does enable a lower
are designed to resist enzymatic degradation and remain
active. In other words, they go through the guy and the
liver and are still there, which is both good and bad.
They can have bad effects on the liver and can cause
severe psychological side effects, especially a
debilitating depression.(1) Women report significant
increases in levels of tension/anxiety and depression on
medroxyprogesterone acetate (Provera) so it's having the
opposite effect of bio-identical progesterone in
balancing estrogen.(4) Progestins don't copy the biologic
activities of progesterone directly.(9) They sort of fill
the same receptors, but then they go on and fill some of
the androgen receptors too. Norethinodrone acetate
(Aygestin) in particular has unintended consequences,
since it's made from testosterone. Progestins work
against estrogen's cardiovascular benefits and can
bringon glucose intolerance.(9) Basically, the side
effects are strong, they don't always bring balance to
the progesterone/estrogen ratio, and the doctors who say,
no progestins, are probably right.
Are there other ways to
affect the progesterone/estrogen ratio?
High levels of boron
are a bad thing for the progesterone/estrogen ratio. It
affects the absorption of calcium, magnesium, and
phosphorus, but worse it increases estrogen production
(and even those of us in the Hormone Jungle are producing
some estrogen). So don't add boron.(35)
It's not going to be
news that eating more vegetables, fruit, and whole grains
and less saturated fat, simple carbohydrates, and sugar
is going to improve your sense of balance. Potassium is
important for water retention and present in this diet.
Yogurt too will help--it helps create healthy intestines,
so the hormones can be processed well.
Stress has a bad effect
on the progesterone/estrogen ratio, just as it has a bad
effect on everything else. In particular, the adrenal
glands under stress can grab progesterone out of the
blood stream and turn it into cortisol, the damaging
stress hormone.(35) Stress increases levels of
aldosterone, which increases fluid retention while
lowering progestesrone. And stress lowers the feel good
endorphins that progesterone can increase.(16)
As usual in the Jungle
it plays a large role in negotiating hormonal balance and
estrogen uses it up in its processing. So, supplements of
it will help too.
Progesterone out of
balance can lower vitamin B6 levels even more than
estrogen alone. B vitamins help maintain liver health
too. The liver needs B vitamins to break down estrogen.
If it can't break down estrogen, the levels of estrogen
increase.(16) With B vitamins low, prolactin increases,
leading to more breast tenderness. Vitamin B6 and zinc
lower prolactin. So supplements with a B vitamin complex
will help with the ratios and the sense of
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