In subject area: Pharmacology, Toxicology and Pharmaceutical Science
Hormone inhibitors are substances that interfere with hormone action, such as an androgen hormone inhibitor that inhibits 5-alpha reductase, thereby reducing the conversion of testosterone into dihydrotestosterone (DHT) and lowering serum DHT levels.
AI generated definition based on: Mosby's Dental Drug Reference (Eleventh Edition), 2014
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Hormonal therapy applies to cancers that are either sensitive or hormone-dependent for development. There are three major types of the hormonal therapy based on the type of cancer (Cancer Research, UK)
1. Breast cancer hormone therapy: Estrogen (ER) and progesterone (PR) are the two essential hormones that influence the development of the breast. The hormone receptors for ER and PR are overexpressed in breast cancer, indicating the role of these hormones in breast cancer development and progression. Approximately 25% of breast cancer patients have been diagnosed with hormone-dependent receptor positive breast cancer in premenopausal women.
There are three different types of hormonal therapy for breast cancer.
i. Competitive inhibitor of ER receptor that lowers the level of ER and PR. It is also known as selective ER receptor modulator (SERM). The most typical example of this class is tamoxifen, also the most widely studied drug for hormonal therapy in breast cancer. Tamoxifen has become the gold standard for hormonal therapy for breast cancer. The other well-known agents of the SERM family are toremifine raloxifene and fulvestrant. Toremifene is similar in structure, except for chlorine at 4th carbon and function. However, toremifene has not been approved by US FDA for adjunct therapy. Conversely, fulvestrant is an ER antagonist which has the higher affinity for ER receptor, compared to tamoxifen. The overall response of fulvestrant is similar to that of tamoxifen.
ii. Ovarian ablation or suppression: The suppression of ER and PR hormone by removing the ovaries is the oldest known therapy for hormone-dependent breast cancer. However, this can be currently achieved by pharmacological agents that can suppress the production of ER and PR. Aromatase inhibitors (AIs) and luteinizing hormone (LH) inhibitors are the most common examples of this class. AI block the ER level by inhibiting the enzyme aromatase. The most recently approved AIs are anastrozole, letrozole, and exemestane, which have been found useful in postmenopausal women with ER-positive receptors. At menopause, the ovaries cease the production of ER, but the adrenal gland continuously produces the androgen, which is converted back to ER by enzyme aromatase present in muscle, breast, and adipose tissues. A high level of aromatase activity has been observed in postmenopausal women. Accordingly, AI is the preferred choice for hormonal therapy in postmenopausal women.
Figure 16.4. The preferred choice of hormonal agent.
LH blocker is an agent that blocks the production of LH in the pituitary, which stimulates the production of ER and PR. Goserelin (Zoladex, AstraZeneca) is the only US FDA-approved LH blocker for hormonal therapy for breast cancer. Goserelin is the highly potent LH inhibitor which is readily metabolized by hydrolysis and excreted in urine.
iii. Sex steroid therapy: The administration of ER and progestin in postmenopausal women has a long history. Progestin has been reported more efficient compared to tamoxifen in postmenopausal women. However, this therapy has severe side effects, such as weight gain, nausea, vaginal bleeding and lower quality of life.
2. Prostate cancer hormonal therapy: Prostate cancer is the most reported male cancer that depends on the male hormone testosterone for its growth. The LH blocker, antiandrogen, and gonadotrophic release hormone (GnRH) blockers have been used for hormonal therapy in prostate cancer to lower the level of serum testosterone. Interestingly, low level of testosterone has also been linked to prostate cancer. Among all hormonal therapies, GnRH blockers have been widely accepted. GnRH blockers render the signal in the hypothalamus of the brain to stop the production of LH, which controls the production of androgens. The list of the agents approved by FDA has been summarized in Table 16.7.
3. Ovarian and womb cancer hormonal th
