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PCOS - Polycystic Ovary Syndrome

Lesson 2 of 6

Oversimplified Primer on the Endocrine System

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Normal Endocrine Function

Let’s start by defining a few of the terms and processes of the endocrine system which will come in handy as you make your way through this course.

For the body to function, cells have to communicate with one another. The endocrine system is a type of communication system whereby cells communicate through chemical messengers known as hormones. For instance, when your brain produces the hormone adrenaline, it prepares your body for action.

Hormones are transported by the blood from the cells that produce them to the rest of the body. Cells pick up the hormonal message when the hormones bind to their receptors, after which the cell initiates processes that lead to an action. That action may be to start (positive feedback) or to stop (negative feedback) producing a different type of hormone.

When any step in this process (e.g. cells don’t produce hormones; hormones don’t bind to the receptor; receptors are bound to another substance) is disrupted, the body is unable to complete the task.

Endocrine System and Fertility

Hormones are at the heart of how the reproductive system functions. In women and individuals with ovaries, the “hypothalamic–pituitary–ovarian axis” is central. Here, two structures in the brain (the hypothalamus and pituitary gland) release hormones that tell the ovaries when to produce an egg, and the uterus when to prepare for an embryo to implant.

Specifically, the hypothalamus releases a hormone called gonadotropin releasing hormone (GnRH; we’ll come back to this as its role is important for women with PCOS) that signals the pituitary gland to produce hormones called “gonadotropins.” There are two types of “gonadotropins”, the hormone follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Both are critical for a person to conceive and carry.

FSH and LH act on cells in the ovaries, and together, their actions promote development of a dominant follicle (a structure in the ovary) that eventually releases a mature egg. Once FSH and LH act on the cells in the ovary, other hormones (e.g. estrogen, progesterone, aromatase) are produced that play important roles in regulating fertility.

Hypothalamic-Pituitary-Ovarian Dysfunction Theory of PCOS

The ways in which the fertility endocrine system can be disrupted for women with PCOS are multiple and can be difficult to follow. Let’s look at one example.

Let’s start with the two gonadotropins produced by the brain: LH and FSH. These are the hormones that signal the ovaries to develop follicles, and in turn, develop mature eggs.

Specifically, LH stimulates the ovaries to produce hormones called “androgens” which eventually must be converted to “estrogens” (critical to help the follicles in the ovary to release a mature egg). FSH stimulates the production of aromatase, the enzyme responsible for the conversion of androgens to estrogens—a process known as aromatization.

In some women with PCOS, the brain produces a lot of the hormone GnRH (which we mentioned above), resulting in an overproduction of LH and in turn this produces more androgens than can be converted to estrogens. The result of this increased androgen level is that the follicles in the ovary have a harder time developing and producing viable, mature eggs.

There are other ways in which women with PCOS may have their fertility endocrine system disrupted. Testing and symptoms may reveal where the breakdown has occurred and which approach your doctor chooses to take.

Fertility Drugs You May Hear About

In the following chapter, you’ll learn more about medications and the approaches aimed at improving conceptions rates for women with PCOS.

Clomiphene Citrate (often referred to as “Clomid”)

When the brain senses small amounts of estrogen in the body it stops producing FSH and LH. Clomiphene citrate binds to estrogen receptors in the brain, and by occupying those receptors, FSH and LH production resumes. When FSH and LH are being produced in proper amounts, they induce a follicle in the ovaries to develop and to release a mature egg.

Letrozole

Letrozole, an aromatase inhibitor, stops estrogen production altogether by blocking the conversion of androgens to estrogens. As such, estrogen’s interference with FSH and LH production ceases and ovarian follicle development continues.

Gonadotropins

Gonadotropins mimic the FSH and LH hormones that a person naturally produces and by introducing more into a person’s body, they signal to the ovaries to develop more follicles which in turn produce more mature eggs.