POLYCYSTIC OVARIAN SYNDROME

Hyper-LH obesity syndrome


Polycystic Ovarian Syndrome (PCOS) is a particular pattern of sex hormone dysregulation, and it’s the most common endocrine disorder in women. It gets its name from the numerous cysts that appear on the ovaries, but it’s important to know that the cysts are a symptom of PCOS and not the cause. There is still scientific debate regarding the precise mechanism of PCOS. But at its core, PCOS refers to having too much LH (lutenizing hormone, which creates androgens) and too little FSH (follicular stimulating hormone, which creates estrogens). So in PCOS, there are too many androgens. High androgens leads to hirsutism (male patterned hair growth) and virilization (male secondary sex characteristics). One of the defining features of PCOS is that ovulation is messed up, which leads to infertility. It also causes fatigue, mood swings, abnormal sex drive and weight gain. 


Obesity is important in PCOS. Let's start with fat cells. Adipose cells create estrogen (specifically they synthesize estrone, the weakest of the estrogens). While estrone can contribute to negative feedback (less FSH release), it’s simply too weak to create the big LH spike that drives ovulation. So no ovulation occurs. Without ovulation, the follicle doesn’t degenerate into the corpus luteum (so no progesterone). The follicle persists. Driven by estrone, it grows into a cyst. One more problem with estrone is that it also impacts the uterus, and unopposed estrogen increases the risk of endometrial cancer.  Obesity and insulin resistance are a big part of PCOS, which is why weight loss is one of the primary treatments. Not everyone with PCOS is obese, but the classic PCOS patient is overweight. This is a nasty feedback loop, because obesity is both a symptom and a cause of PCOS.


All patients are encouraged to lose weight. In patients who aren’t planning to conceive, you should give birth control (to rebalance the estrogens) and metformin (to reduce insulin resistance). If the virilization is especially problematic, anti-androgen drugs like Spironolactone, Finasteride and Flutamide  may be helpful. To treat infertility, the gold standard drug is Letrozole, the aromatase inhibitor. The second line agent is Clomiphene, which tricks the hypothalamus into thinking that it needs to make a lot of FSH. 

Black is the normal function

Red is the PCOS pathway

Gold is for drugs

OVARIAN TORSION

Gonad attack


Ovarian Torsion refers to when an ovary’s blood supply twists on itself until it’s compressed. The absence of blood flow leads to infarction, like a heart attack of the gonad. Torsion is rare under normal circumstances, but it becomes more likely whenever there’s an adnexal mass (ovarian cyst or tumor). I guess that a mass distorts the architecture of the pelvis in such a way that it allows the ovary to spin. Ovarian ischemia causes sudden unilateral lower abdominal pain accompanied by nausea and vomiting. The ovarian artery can sometimes torse and un-torse spontaneously, leading to intermittent attacks of pain. That can make it pretty difficult to recognize torsion. Ovarian torsion is a medical emergency, just like its cousin, testicular torsion. Without prompt surgical detorsion, the ovary will be permanently lost. The diagnosis is intuitive -- you look for the absence of blood flow on a doppler ultrasound

OVARIAN CANCER


Benign 

Cancer

EPITHELIAL TUMORS are the most common tumors of the ovaries. The ovaries are surrounded by a layer of epithelium that extends along the fallopian tubes. The epithelium is damaged every time that ovulation occurs, as the egg literally explodes out of the gonad. Therefore, women who’ve had lots of periods (early menarche, late menopause, nulliparity, never taken birth control) are at higher risk. Most patient are post-menopausal. Other risk factors include BRCA1, BRCA2, Lynch syndrome, PCOS, endometriosis and old age. While the other ovarian tumors are notorious for secreting hormones, the epithelial tumors are pretty inert. Of note, they do secrete a marker called CA-125. Since a handful of other ovarian problems (endometriosis) can elevate the CA-125, it’s not useful as a screening test, but it does come in handy when tracking the progression of an epithelial cancer over time. They like to spread locally, especially into the peritoneum. Peritoneal invasion causes vague symptoms like abdominal distention, bloating, early satiety, fatigue and weight loss. Modern research suggests that most of these tumors probably originate on the fallopian tubes, which is why salpingectomies are increasingly recommended over tubal ligations. 


GERM CELL TUMORS are descended from the egg stem cells. They contain blueprints for many different tissues (fetus, placenta, yolk sac, etc). Each one of those blueprints can become cancerous. Average age of onset is younger than epithelial cancers.


STROMAL TUMORS are descended from anything else in the ovary. 


METASTASES aren’t especially common to the ovaries, but here are two high yield examples.