What is hormone therapy?

What is a hormone?

To fully understand hormone therapy, you must first understand what hormones are and how they work. Hormones are chemicals produced by specific cells in the body called endocrine glands. 

Hormones are carried in the bloodstream and act on targeted cells with specific receptors. They thus participate in the function of certain organs (the ovaries and testes secrete sex hormones, the thyroid secretes thyroid hormones, the pancreas secretes insulin, etc.) and intervene in certain biological processes (growth, regulation of blood sugar levels, regulation of blood pressure, etc.). 

They are the messengers of the endocrine system.

What is hormone therapy?

Not to be confused with contraceptives and hormone replacement therapy (for menopause), hormone therapy is an anti-hormonal treatment that aims to block the production or activity of natural hormones produced by the body and known to stimulate the growth of various cancers.

Unlike chemotherapy or radiotherapy, it does not directly destroy cancer cells, but inhibits the hormones that cause their growth.

It is used in cancers considered to be hormone-receptor-positive, i.e. those whose cells have hormone receptors on their surface. Among them, the most common are breast cancer and prostate cancer.

Hormone therapy: how does it work?

Hormone therapy can block the stimulating action of hormones in 3 different ways:

• Blocking the production of hormones at the central level by inhibiting the secretion of LHRH (the hormone that stimulates the pituitary gland) in the hypothalamus, LH/FSH (gonadotropin hormones secreted by the pituitary gland in response to LHRH, which stimulates the ovaries and testes) and ACTH (the hormone that stimulates the adrenal gland to release cortisol) in the pituitary gland. The hypothalamus and pituitary gland are both located at the base of the brain;
• Block the production of hormones at the peripheral level (inhibition of the estrogen secretion by the ovaries, testosterone by the testes and androgen by the adrenal glands);
• Blocking hormone receptors at the tumor cell level.

Who is hormone therapy for and when should it be started?

The choice of therapeutic strategy to treat cancer is based on the patient's age and life expectancy, overall condition, anatomical and pathological findings (the Gleason score for prostate cancer, for example), biological data (estrogen receptor (ER) status for breast cancer and prostate-specific antigen (PSA) levels for prostate cancer), imaging data (ultrasound, mammography, MRI, etc.), biopsies, and finally, the TNM classification (a standard classifying the extent of spread of cancer, describing the size of the tumor, the lymph nodes involved, and metastasis).

In cases of breast cancer, hormone therapy is generally indicated starting at stage II when the cancer is invasive (about two-thirds of cancer cases are detected at this stage by mammography) or locally advanced (i.e. the lymph nodes are affected) and when it is hormone receptor-positive (HR+). It is often used after surgery and radiotherapy and is usually taken for at least 5 to 10 years.

In cases of prostate cancer, hormone therapy is indicated when the cancer is locally advanced or has metastasized. The goal is to lower levels of testosterone to < 3ng/mL. It is commonly used before chemotherapy and when the estimated life expectancy is more than 10 years.

Hormone therapy and breast cancer

Most breast cancer cases are hormone-receptor-positive (HR+) and are ER-positive (ER+) (meaning that they have estrogen receptors).

Hormone therapy has dual objectives: to increase relapse-free survival and to increase overall survival after surgery and/or radiotherapy.

Treatment depends on whether or not the patient is in menopause.

If the patient are pre-menopausal, the following drugs are used:

• Luteinizing hormone-releasing hormone (LHRH) analogs or agonists, or drugs that stop the body's signal to the ovaries to produce estrogen, thus causing temporary menopause. Common LHRH analogs include Goserelin - ZOLADEX® and Leuprolide-LUPRON®.
• Or selective oestrogen receptor degraders (SERDs) (TAMOXIFEN, Fulvestrant - FASLODEX®), blocks and damages oestrogen receptors, with a high affinity for breast cancer cells.

If the patient is post-menopausal, aromatase inhibitors (AIs) (Exemestane - AROMASIN®, Letrozole - FEMARA® and Anastrozole - ARIMIDEX®) are used. Aromatase is an enzyme that allows the body to continue to produce estrogen, through the transformation of androgens, in postmenopausal women. Inhibition of aromatase reduces the level of circulating estrogen and estrogen receptors (ERs)

Hormone therapy and prostate cancer 

Prostate cancer is hormone-dependent, dependent on testicular (90%) and adrenal (10%) androgens. These androgens stimulate the growth of prostate tissue and tumor cells. The two most abundant androgens in men are: testosterone (whose active form is dihydrotestosterone, or DHT) and DHEA (Dehydroepiandrosterone, or androstenolone).

Hormone therapy can be done in two ways:

• Surgical castration (bilateral orchiectomy)
• "Chemical" or "medical" castration, using medication

Different drug treatments can be considered:

• Luteinizing hormone-releasing hormone (LHRH) agonists (Buserelin - SUPREFACT®, Goserelin - ZOLADEX®, Leuprolide -LUPRON®, and Triptorelin - TRELSTAR®) cause pituitary desensitization and thus decrease testosterone and DHEA secretion. When LHRH agonists are first given, a temporary peak in testosterone levels (a "flare") can be observed, therefore anti-androgens are co-prescribed for 2 to 3 weeks.  
• Anti-androgens prevent testosterone from attaching to androgen receptor proteins in the prostate (non-steroidal: Nilutamide - NILANDRON®, Bicalutamide - CASODEX®) and to its hypothalamic receptors.
• LHRH antagonists (Degarelix - FIRMAGON®) bind to pituitary receptors and immediately block the secretion of LH and FSH and thus testosterone.
• Anti-androgens used as a second line treatment in cases of castration-resistance (Abiraterone - ZYTIGA®), or when the cancer is still growing despite low testosterone levels from an LHRH agonist, LHRH antagonist, or orchiectomy. These block an enzyme called CYP17 which helps prevent androgen secretion. They are often co-prescribed with corticosteroids (Prednisone).
• Estrogens may be used if other hormone treatments are no longer working. Used as second-line treatment in the event of hormone resistance, they act on hypothalamic receptors and block the pituitary release of LHRH, thus reducing testosterone secretion (Estramustine phosphate - ESTRACYT®, EMCYT®).

What are the side effects of hormone therapy?

Adverse effects of hormone therapy are consistent with the effects of menopause (decreased estrogen and progesterone secretion) and andropause (decreased testosterone secretion).

As such, immediate side effects include hot flashes (ease by drinking cold beverages, avoid alcohol and coffee, keep rooms cool), muscle and joint pain (exercise and use painkillers such as paracetamol), dryness of the skin and mucous membrane (use soaps with a proper PH level), hair loss, thromboembolism (wear compression stockings, especially during long drives or flights), digestive disorders such as nausea, weight gain (pay close attention to diet, lower sugar and fat intake and increase protein), fatigue (exercise regularly, avoid caffeine after 4PM) and libido disorders and erectile dysfunction (injections into the corpus cavernosum at the base of the penis are possible with Alprostadil - CAVERJECT®, MUSE®, EDEX® and if erections are weak, Sidenafil - VIAGRA® can be taken).

In the long term, hormone therapy may potentially increase the risk of uterine cancer depending on the duration of treatment, the age and menopausal status of the patient, with a low absolute risk before the age of 55, and an increased incidence in older women. But this does not seem to affect survival, thanks to early diagnosis and favorable biology (regular gynecological check-ups are therefore necessary). It may also increase the risk of osteoporosis or of fracture (calcium and vitamin D supplements are important).

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