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Sunday, October 21, 2007 

Medical Question #2. Ovarian Cysts

Ms. L wrote me:

Hello Dr. Kavokin,

I was reading some of your literature and found it to be quite informative. I have a question that perhaps you may be able to answer: If a woman's ovarian cyst ruptures, (especially multiple cysts from PCOS) can these ruptured cysts become an infection?

Hi, MS. L

Short answer: anything can become infected. Though I do no think ruptured ovarian cyst becomes infected very often, did not hear about that. I will look more literature and probably place the answer on my website.

Sincerely,
Alex

OK. I looked the literature.

I didn't do very extensive literature search. Should admit. Anyway, some available books mention that ovarian cyst may become infected. However the infection is not described as the main complication in ovarian cyst rupture.

Also, I don't remember that anybody told me otherwise. Maybe there is some specialized article that says: the condition happens in one point three percent of cases with Standard Deviation of half percent. I don't know exact percentage. Need to look more. PubMed service did not give many abstracts on PCOS + infection.

Anyway.

So how would it look alike?

A young woman comes to ER. She is premenopausal. She complains on mild (or maybe severe) pain in her belly. ER Doctor takes history. The woman also mentions changes in her menstrual interval. Let's say regular is 28 days. Last one was delayed.

Physician puts gloves, puts jelly on gloves. Then he puts his two fingers into the female vagina. The other hand is on belly. Then he starts to palpate.

It is named pelvic exam. Modest name. Though in Russia it is named vaginal exam, which it is.

Is it a common type of exam? Depends. They usually send you to CT (computer tomography) scan if there is severe abdominal pain. Charge 1000. Boom. Done.

Exclude the price. Exclude delay in reading (somebody should look and interpret what is going on). Exclude radiation. CT scan gives better picture than just poking your belly.

CT scan helps to diagnose abdominal pain of uncertain origin. You can really image what is going on. Though, there are cases when physical exam gives more clues. Physical exam must be performed always. Pelvic exam is somewhat a special one.

I remember how I performed a pelvic exam in medical school. It is actually difficult even just to insert two fingers into vagina first time. Female Gynecologist asks me: "So, what do you feel?" Patient goes the same, encourages me: "What do you feel, what do you feel, do you feel it?"

I guess she felt a sort of museum artifact. Heck, I did not feel anything.

Well. Actually I felt something - aside from uterus - something round. I would say 5 cm in diameter (would it be less I probably would not feel it at all) and semi-solid on touch. Also I saw that the patient grimaces. It is tender when I push hard.

It's it. How to say that it was tuboovarian abscess (that it was) for sure, I don?t know. You really need experience to perform this type of exam. Experienced gynecologist can tell almost precisely what is going on.

Let's discuss that woman in ER. She will have tenderness on one side. Physician should be able to feel a mobile cystic mass. (Cyst or rather cystis is Latin for bubble. Palpate is Latin for touch. It means you touch something and feel what it is). What if the pain is severe? It often means that the cyst ruptured. My impression is that modern ER orders CT scan right away. If you are not very sure what is going on, you will go from less expensive methods to more expensive and end up with CT anyway. Ruptured cyst causes significant pain. Here CT is indicated.

Alternatively they may order Ultrasound Exam. Transvaginal ultrasound uses the probe inserted into vagina. Ultrasound is cheaper than CT. Ultrasound visualizes cysts clearly. Though, ultrasound gives less information for excluding other pathology. Ultrasound is also safe from the radiation point of view.

In PCOS ultrasound shows increased number of small cysts in both ovaries. Usually more than five confirms the diagnosis.

Culdocentesis may give some useful information too. The name came from cul-de-sac. It's French I guess. Cul-de-sac is one of the pouches in the pelvis. Centesis means: stick a needle and draw. These days it is considered an outdated method. But if you do not have other machines, it is very useful.

If the content is blood, the ruptured cyst was probably Corpus luteum cyst. If the content is purulent the ruptured thing was probably a tubo-ovarian abscess or other pelvic inflammatory disease (PID). Other abnormal masses can rupture as well. Teratoma gives oily fluid, endometrioma gives "chocolate" old blood.

What is a follicle?

Female body is created for reproduction and childbearing. Oocyte is the start for a new human being in the ovaries. Several layers of specialized membranes surround an oocyte.

The membranes protect the oocyte, help in feeding and nurturing of this small cell. One of layers has a beautiful name Zona pellucida. Pellucida means shiny in Latin.

When the oocyte matures, a small bubble (follicle) filled with special fluid is formed around. In mid-cycle the follicle bursts and the oocyte goes first into peritoneal cavity, next into ovarian tubes (fallopian tubes). The tubes lead into uterus. Tubes, by the way, have special small hair-like things inside - fimbria. They beat in one direction. They propel the oocyte into uterus.

I remember I read somewhere that there are 11000 follicles. When a girl is born, there is no more multiplication of oocytes. After the birth the follicles sit dormant. When the female goes into her reproductive age, the follicles start to grow and mature (one by one).

Only 400 of them mature.

Yeah, it should be like this. Calculate. Average cycle is 28 days. So there are around 12 cycles a year. Women start to menstruate at 13-15 years old. The menopause is around 45-55 years. Total is 30-40 years

Multiply everything together. It should be around 400.

By the way, an interesting thought.

All those discussion about abortion and Stem Cell research. Somewhere in nineteen century the baby was considered the baby when it was born. The church even struggled to admit anything like existence of cells etc. Rare baby actually survived beyond first year. Heck, the hypothesis that human been consists of small cells was actually admitted widely not so long ago. Maybe hundred years ago. Then, all that research happened. People learned how the fetus is created and how it grows. Now the public idea is that fertilized oocyte is already the baby.

Have you seen any oocyte under microscope? Even a human hair near an oocyte looks like a skyscraper near a real human.

Now, if the public perception had shifted this way in several decades, shouldn't we punish all women for that they recklessly loose 400 potential babies during lifetime. Isn't it a crime?

Then, maybe we should punish every man for losing millions of sperms - also potential babies. Where did this idea come from that fertilized oocyte is the baby and non-fertilized oocyte is not? Shouldn't we move the boundary a little bit earlier? Need to think about that.

Anyway.

Ovarian follicle (follicle means small bubble in Latin) usually mature, rupture and release the oocyte that was in this follicle. Sometime the rupture delays. Then ovulation delayes. (Ovulation is rupture and release of the oocyte. Oocyte is the cell that eventually becomes the fetus after sperm gives the genetic material).

Normal cycle is divided into follicular phase (when the follicle grows) and luteal phase. Luteum means yellow in Latin.

When the follicle ruptures (by the way rupture means burst or tearing), the oocyte goes out.

The cavity that left behind (remember it was small bubble) is filled with blood and special cells, producing hormones. These special cells grow in quantity and fill that cavity. These cells produce hormones that help the fertilized oocyte to attach and to grow in the uterus. Because they grow in quantity, they create a yellowish body in the ovary. It is literally yellowish. The name is Corpus Luteum (corpus=body, luteum = yellow).

This is normal cycle.

As we said, the follicle sometime doesn?t rupture (there is a bunch of reasons). A physician should sort out several different conditions. This is an abnormal cycle. If follicle does not rupture it becomes the follicular cyst. Cyst also means bubble in Latin. There are actually plenty of different kinds of bubbles in medical Latin. Big ones and small ones. Normal and abnormal.

OK, the cyst did not rupture. Then what happens?

Well. If cyst doesn't rupture, it usually resolves. That fluid inside the cyst is reabsorbed and the cyst collapses.

However, if the cyst ruptures, it causes acute pain. The pain comes from irritation of peritoneum (lining of peritoneal cavity) with blood and cyst content.

Why it is not painful when a regular follicle ruptures and releases the oocyte? Probably, a regular follicle is too small. In addition it doesn't cause much bleeding.

In contrast the cyst is a really big bubble (sometime 5-10 cm in diameter). If it ruptures, it instantaneously release bunch of special fluid. Plus, there is significant bleeding because there are a lot of blood vessels around to feed.

Significant is of course relative.

For example, take 5-10-20 ml of blood from a patient vein in a hospital daily. He complains about the pain from the needle mostly.

But if you get the same 10 ml of blood into peritoneum... Wow. You will cry. There are plenty of nerve endings. Peritoneum is too touchy-feely. Tender.

Besides, the cyst has high concentration of prostaglandins. Prostaglandins, in their turn, are mediators of inflammation. They should cause significant pain directly and indirectly.

From the other hand bleeding could be really significant. Then it becomes really dangerous.

A physician also should not miss an ectopic pregnancy. Doctor will order a pregnancy test for that. If an ectopic pregnancy starts to bleed, this is really really worrisome. It seems like your blood did not left your body. However the blood is in the abdominal cavity. It left the blood vessels. It is internal bleeding. You die quickly.

Polycystic ovarian syndrome is a little bit different animal actually. Here is some genetic predisposition.

Classically: an overweight young female presents with oligomenorrhea or amenorrhea, anovulation, acne, hirsutism, and or infertility.

What is what? Poly = many. Many, many, many men. So PCOS means bunch of those bubbles in the ovaries. The follicles did not rupture on time, as they should. Oligo means a little. Meno is derived from menses. Rrhea means flow in Latin

So olygomenorrhea = flowing a little bit (less than it should). A- is a prefix that means "No". So, amenorrhea = no flow at all. Hirsutism. I don't remember where it came from, but means hairy or hairiness. Actually excessive hairiness.

Causes of PCOD or PCOS (disease or syndrome) are obesity, genetic predisposition and some other causes of Luteinizing hormone (LH) excess.

There is a self-amplifying cycle:

LH stimulates theca lutein cells. Theca means sort of capsule. Doesn't really matter, just an anatomical term. Those cells are special. They produce androstendione and testosterone. Androstendione and testosterone are actually male hormones. You know, bodybuilders use these hormones to get muscle bulk. You probably heard about those hormones. Sport doping uses testosterone. So, athletes build their muscles and trash their liver.

Rumors say that a famous Hollywood actor used the hormones. Later he got liver transplant. Though he always denied the use.

Anyway, female body converts androstendione into estrone (a weak estrogen). Fat cells do this. Estrone is a female hormone already.

Basically any body produces androgens (andros = man) and estrogens (female hormones). Just the proportion of those hormones makes us male or female.

The cycle happens in normal person as well.

The estrone stimulates pituitary secretion of LH. Pituitary is a small gland in you brain. Pea Size. It's small, but it sooooo powerful.

Pituitary has another name - hypophysis. Hypo means down, phys means growth, so this gland is growing from below the rest of the brain. Pituitary gets bunch of connections from hypothalamus. Hypothalamus means ?below thalamus?? These two areas of brain regulate almost all the hormone production in organism.

Higher levels in brain hierarchy regulate them.

Hypophysis gets a command. Then it produces some intermediate messengers and hormones. The hormones go into blood and control whole body.

Hormones are like orders, like messages to the rest of the body.

Brain may give quick orders: Signals go through the nerves. It is like a phone order or cablegram.

Brain also regulates organism through the hormones. This is like a mail order. Sort of if the brain sends letters by regular mail. The hypophysis is the Post Office in this case.

PCOS kicks in when a woman is obese. There are more fat cells to convert androstendione to estrone. Estrone has such effect that it stimulates pituitary secretion of LH. LH in its turn goes back to those theca lutein cells we discussed and turns them on again, to produce more androstendione, which is again converted into estrone.

Self-amplifying cycle

In addition, that increased level of testosterone causes the hirsutism (she becomes hairy like a male) and acne in female. In a normal person this cycle is probably designed to support the development of fetus. Estrogen helps placenta to grow. Placenta supports fetal growth.

However, in a person with PCOD the cycle is going out of normal control. In this case LH causes growth of the cysts in the ovaries.

Why?

Because the corpus luteum cyst is partially made by overgrowth of those theca lutein cells. LH stimulates theca lutein cells.

Also, women with PCOS have intolerance to glucose (sugar) and resistance to insulin. It means there is a lot of insulin (hormone that helps to utilize glucose mainly).

However excessive insulin does not work. Either receptors to insulin do not work or something else, but the glucose is not utilized. Hence, energy inside the cells drops. Hence, a big pile of other problems mounts. As if it is Diabetes Mellitus. Diabetes is a different topic of discussion. For us, it is worthwhile to mention that people with diabetes are very much prone to any infection.

PCOS causes acanthosis nigricans also. Acantocytes are special skin cells. Nigricans means black in Latin. That thing looks like thickened pigmented skin. When you touch it, it feels like velvet. Usually it happens in axilla, neck, below breast, in inner thigh and vulva. So, mostly all those places where skin folds.

The treatment for PCOS includes different medications: oral contraceptives, progesterone, glucocorticoids, ketoconazole, spironolactone, cyproterone, flutamide, cimetidine, finasteride, ovarian wedge resection, laparascopic electoracutery, mechanical hair removal, etc.

All methods break the cycle of overproduction. The medications are either hormones themself or hormone-like substances that occupy receptor site and prevent regular hormone to work.

The medications act on different levels. Normal hormones have very complicated regulation. There are loops and feedbacks in the pathways.

To suppress a hormone production or action, you give similar hormone or another hormone or non-hormone at all, that goes to the feedback loop and breaks it and so on. It's really long separate discussion.

Basically, you either decrease hormone production or shift ratio toward female hormones.

Another way, the best probably, is weight loss. No fat cells - no conversion of andrgoens etc??You can make conclusions yourself. It's the first line of treatment.

For a simple follicular ovarian cyst (not PCOS) doctor rules out ectopic pregnancy. Then he may send patient home and repeat pelvic exam in 6-8 weeks. Especially, if the cyst was small, less than five cm in diameter.

For larger cysts, doctor would order pelvic ultrasound.

Most follicular cyst will resolve on their own in six to eight weeks. Though, a physician may give oral contraceptives. Again, this suppresses stimulation of cyst by hormones from the hypophysis. The hormones are named gonadotropins.

If the cyst is still there after 6-8 weeks, a suspicion arises that the cyst maybe malignant. Then doctor orders other studies. CT scan. Physician may perform surgical procedures also. He looks what is this cyst really.

Corpus luteum cyst is usually not treated. However, oral contraceptives may be used.

Rupture of any kind of those cysts leads to another story. Acute pain, bleeding into peritoneum. Sometime bleeding is very severe and is true emergency. You need also to distinguish other process in the abdomen. For example, appendicitis looks similar. You can treat mild case of non-complicated cyst rupture with just observation. Appendicitis almost always requires surgery.

There are many other problems arise. Surgeon scratches his head: what's going on? Is this this or is this that? Here is the CT scan gives big advantage.

Now, going back to the question of Ms. L.

If the cyst was infected, I don't' see a reason why a ruptured cyst wouldn't become infected. Cyst content is very nutrient-rich. Remember? All those cells and their products are dedicated to feeding the oocyte (future baby). Should be very tasty for any bacteria.

Rupture may cause significant bleeding as well. This blood is also different from the blood in your vessels.

This blood is sitting in the pelvis, not moving, quickly clotting. Clotting prevents entry of white blood cells. "No flow" prevents entry of antibodies. Absence of flow prevents entry of other protective chemicals (complement etc).

So, it is very nutrient-rich media for bacteria growth.

They can go wild. Why not? If a female had another pelvic infection before, that infection can flare up. In a normal person peritoneal cavity should be sterile. However, any gynecological or gastrointestinal infection may supply bacteria. Now, mix these bacteria with the content of the leaking cyst. It just destined to become infected.

Actually Ms. L later answered her own question in another e-mail. She had cysts multiple times and they became infected several times.

So, to answer the question: Will the ruptured cyst become infected? Not necessarily. Rather not. Can it become infected? Yes.

Aleksandr Kavokin MD/PhD, Phila appendicitis_disease@yahoo.com http://www.appendicitis.uni.cc/ Aleksandr Kavokin, MD1994 Russia,PhD1997 Russia - Immunology and Allergy, postdoc at Cancer Center at Med U of South Carolina, postdoc at Yale - Cardiology, Molecular Medicine. http://kavokin.com http://www.geocities.com/aging_rejuvenation/ http://www.geocities.com/appendicitis_disease/

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