Aromatase inhibitors

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Introduction0:00–0:27

Aromatase inhibitors, or AIs, are a type of medication used to treat breast cancer in postmenopausal people. However, they should only be used if the breast cancer is positive for estrogen receptors.
Breast cancer, or breast carcinoma, is an uncontrolled growth of epithelial cells within the breast. It’s the most common cancer in female individuals, and the second leading cause of cancer deaths after lung cancer.

Physiology0:27–1:24

Breasts are made up of 15 to 20 lobules, and inside each of these lie a bunch of grape-like structures called the alveoli.
Zooming in on the alveoli, there’s a layer of alveolar cells that secrete breast milk into the lumen, which is the space in the center of the gland.
These alveolar cells have receptors for certain hormones like, estrogen and progesterone, which are released by the ovaries, and prolactin which is released by the pituitary gland.
These hormones stimulate the alveolar cells to divide and increase in number, which makes the lobule enlarge. Just like healthy alveolar cells, some breast cancer cells have hormone receptors that allow them to grow in the presence of the hormones.
When breast cancer cells have estrogen receptors, the cancer is called an ER-positive carcinoma. In this case, hormonal therapy is useful for adjuvant treatment, and includes medications which block the formation or effects of estrogen.

Mechanism of Action1:24–2:45

Aromatase inhibitors block the formation of estrogen by inhibiting the aromatase enzyme that converts androgen to estrogen.
Now, before menopause, estrogen is mainly synthesized by the ovaries, where there’s a lot of androgen waiting to be converted.
And the amount of aromatase enzyme in the ovary depends on the stimulation by gonadotropin. So, even if we gave this medication to premenopausal women with breast cancer, gonadotropin would induce synthesis of more aromatase, which would synthesize more estrogen.
However, in postmenopausal women, estrogen is synthesized by other tissues, like the adrenal glands and fat tissue. Here, aromatase levels don’t depend on gonadotropin, so AIs can decrease aromatase and lower estrogen levels in postmenopausal women.
Now, there are two main types of aromatase inhibitors. Type I AIs are steroidal agents that irreversibly bind to aromatase and prevent androgens from binding.
So they’re competitive inhibitors. Type II AIs, on the other side, are non-steroidal agents.
They’re also competitive inhibitors, but in this case, they bind reversibly. Non-steroidal AIs include anastrozole and letrozole, while exemestane is a steroidal inhibitor.
All these medications are given daily peroral. Fortunately, in general these medications are well tolerated.

Side effects2:45–3:49

However, since estrogen has a protective effect on the cardiovascular system and helps sustain bone density, people on aromatase inhibitors are deprived from its protective effects.
This can increase the risk of developing cardiovascular diseases and osteopenia, or even osteoporosis, especially in the lumbar spine and hip, which can lead to fractures.
Bisphosphonates should be administered together with AIs to prevent such events. The decrease in estrogen levels also accounts for symptoms similar to those that precede menopause, like hot flashes, night sweats, vaginal dryness, and loss of libido.
Joint symptoms like arthralgia, arthrosis, arthritis, and disk herniation can also occur. Letrozole can also cause nausea, and hair thinning, but it has less cardiovascular side effects.
Exemestane can cause nausea, diarrhea, fatigue, as well as visual disturbances. Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts!

Memory palace3:49–5:16

We’ll set the scene in a perfume shop since we’re talking about aromatase inhibitors. So the class I steroidal drugs that irreversibly bind to the enzyme will be represented by the staff behind the counter, since they can’t leave the store.
The customers who can come and go will represent the class II non-steroidal drugs that bind reversibly. For the staff, we have the Russian princess Anastasia for anastrozole as the sales lady.
Next to her, there’s a janitor lady cleaning up litter for letrozole. The customer at the counter is a well-dressed executive for exemestane.
For side effects, we can look at the items on the counter. First, there’s a heart-shaped perfume bottle covered in blood vessels to represent the increased risk for cardiovascular disease.
Now, this special perfume is made from bones, so there’s a stove cooking some broken bones right on the counter. This represents menopausal symptoms such as hot flashes and osteoporosis.
Some of the bones form an intact joint, which is very red and this represents arthritis. Okay, for some of the drug-specific side effects, the executive is wearing an eyepatch, since exemestane causes visual disturbances, while the janitor lady has a bald spot because letrozole causes hair loss.
All right, as a quick recap… Aromatase inhibitors, or AIs, are a type of medication used to treat ER-positive breast cancer in postmenopausal women.

Review5:16–6:07

They block estrogen synthesis by inhibiting the aromatase enzyme that converts androgens to estrogens. Type I AIs like anastrozole and letrozole are steroidal agents that irreversibly bind and inhibit aromatase.
Type II AIs are non-steroidal agents like exemestan that reversibly bind to aromatase. These medications are well tolerated, but can also increase the risk of cardiovascular disease, osteopenia or osteoporosis, joint symptoms, and menopause-like symptoms, such as hot flashes, night sweats, vaginal dryness, and loss of libido.

Mind Map6:07–6:26

But wait, there’s more: Here’s a mind map with all of the mnemonics. Go ahead and pause the video so you can test yourself to see what you remember.
Stay tuned for the answers after the credits.