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Hormone balances play an important role in the function of the gallbladder, but the way the gallbladder responds to hormones, even the same hormones, is very different in men and women.

In men, the gallbladder becomes more and more sensitive to the neurotransmitter acetylcholine with age. The central nervous system releases acetycholine when we wake up and when we experience pleasure. By the time you reach your 60's, probably, if you are a man, or, whether you are a man or not, you probably know a man who was chomping down on his favorite food when he suffered an excruciating gallbladder attack. Acetylcholine increases the gallbladder's tone. If there are gallstones, it clamps down around them and causes excruciating pain. Men in their 70's and older become so sensitive that they can have attacks of acalculous cholecystitis, gallbladder attacks without even having any gallstones.

In women, the gallbladder becomes less and less sensitive to acetylcholine with age.

Women are less likely to have gallbladder attacks when they are eating their favorite foods than men, especially as they get older. However, women are more likely to develop gallstones than men all through their reproductive lives. That's because of the way the gallbladder reacts to a hormone much more abundant in women's bodies, progesterone.

Progesterone is the hormone that thickens a woman's uterine lining in the second half of her menstrual period. It also "calms" the lining of the uterus during the second half of her period. If a woman is going to get pregnant, the egg must be fertilized within about the first 24 hours after ovulation. Then the fertilized egg must implant itself in the lining of the uterus. This is more likely if the lining of the uterus is growing, and progesterone levels increase after ovulation if the egg is fertilized or if it isn't. However, there is also less movement in the uterine lining to give the fertilized egg a chance to establish itself in the womb.

Progesterone doesn't just reduce smooth muscle activity around the uterus. It also reduces smooth muscle activity around the gallbladder. The bile and cholesterol salts that the liver pumps into the gallbladder are less likely to drain into the bowel and more likely to stay in place. When bile doesn't move, in this condition called gallbladder stasis, the salts and cholesterol in the fluid are more likely to form crystals that become stones. What this means is:

  • Just before and during a woman's period, her gallbladder is most likely to make stones.
  • The younger a woman is, the more likely her gallbladder is to contract around gallstones around the time of her period. Intense pain may result, although PMS symptoms can make it difficult to tell exactly what the pain is. 
  • After a woman's period, any gallstones will probably still be there. They won't cause as much discomfort for a couple of weeks, until she is in the second half of period once again.

Women's bodies create huge amounts of progesterone during pregnancy. That's why women are especially likely to have gallstone attacks when they are pregnant. Sometimes it is simply is necessary to get medical treatment. However, there are some things that women can do to lessen the effects of menstruation on gallbladder function.

The way progesterone causes smooth muscles to become "quiet" is by activating a specific enzyme known as CYP3A4. Women can avoid activating this enzyme even more by:

  • Avoiding chili peppers and hot sauce. The capsaicin in hot peppers in this case isn't acting on the stomach. It's acting on the liver and activating CYP3A4, which increases the effects of progesterone.
  • Avoiding St. John's wort. This common herbal depression treatment also activates the enzyme in question.
  • Minimizing consumption of grapefruit, apples, and onions, which contain quercetin, which works on the enzyme.

Certain medications also increase the risk of gallstones. Ask your pharmacist if any of the drugs you are taking is a CYP3A4 inducer.

There's one caveat to this approach to managing gallbladder symptoms. If you are trying to get pregnant, you will be slightly less likely to conceive if you manage gallbladder problems this way. However, just "avoid avoiding" capsaicin, St.John's wort, and quercetin-rich fruits and vegetables for a few days around the time you ovulate. If you do this, you will give a fertilized egg a chance to implant.

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