What is Tamoxifen?
Tamoxifen is an anti-estrogen drug, known for its role in breast cancer treatment. It is a competitive estrogen receptor inhibitor, meaning that it competes with the hormone estrogen in binding to its receptor in the body [1, 2].
Some breast tumours express the estrogen receptor (we call these estrogen receptor-positive, or ER-positive breast cancers), which, when activated by estrogen binding, promotes the growth of the tumour [3]. Therefore, blocking the receptor with tamoxifen is desired when treating an ER-positive breast cancer.
Uses of Tamoxifen
Tamoxifen is primarily used in the adjuvant endocrine therapy of breast cancer in post-menopausal women. The word 'adjuvant' means that tamoxifen is administered alongside other drugs, for example chemotherapy.
Tamoxifen can also be used in women with anovulatory infertility (infertility due to lack of ovulation), due to its effects on the secretion of pituitary gonadotropic hormones (these are hormones that maintain the function of the reproductive system).
It is also being evaluated in clinical trials as an adjuvant therapy for premenopausal patients with either node-positive or node-negative disease [1, 2].
Outcomes Following Tamoxifen Treatment
Tamoxifen is a very effective component of breast cancer therapy. Tamoxifen treatment markedly improves survival in patients with ER-positive breast cancers, and lowers the chance of cancer developing in the opposite breast by up to 50% [4]. Tamoxifen is also an effective drug in preventing breast cancer, indicated to patients with a high genetic risk for breast cancer (such as mutations in BRCA genes). Furthermore, tamoxifen has been shown to reduce recurrence of breast cancer following a successful treatment by 40 - 50% [3].
Adverse Effects of Tamoxifen
Tamoxifen is generally well-tolerated, and therefore presents as a good treatment option. However, the drug does have several potential adverse effects. These can include:
- increased risk of endometrial cancer,
- increased risk of liver disease,
- increased risk of blood clotting disorders,
- ocular toxicity [4, 3].
The risk of endometrial cancer is especially prevalent in pre-menopausal women - it is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen [3]. Rarely, tamoxifen can also cause arrhythmia [5].
Tamoxifen Use in Men and Fitness
Long-term misuse of androgen therapy (synthetic anabolic steroids) in order to enhance exercise performance is gaining prevalence in the fitness community, however, it is highly disruptive to the body's hormone balance. As the body is presented with large doses of testosterone, it tries to compensate and restore the hormone balance by synthesising estrogen. This is a cause of some adverse effects of androgen therapy, such as gynecomastia.
Due to its action of blocking the estrogen receptor, tamoxifen may be used to counteract these side effects of androgen therapy. However, the evidence supporting its use in fitness is limited and primarily based on its potential to increase the endogenous production of androgens in males [6].
What is Anastrozole?
Anastrozole is a non-steroidal inhibitor of human placental aromatase, an enzyme which is involved in estrogen synthesis [7, 8].
Anastrozole works by inhibiting the aromatase enzyme, which is responsible for the final step of estrogen biosynthesis in peripheral tissues. These tissues are the main source of estrogen in postmenopausal women. By inhibiting this enzyme, anastrozole effectively suppresses estrogen production [7].
Uses of Anastrozole
Given its effect on reducing estrogen production, anastrozole is used in the treatment or ER-positive breast cancer in post-menopausal women as an adjuvant therapy.
Additionally, anastrozole can be used in treatment of male infertility in patients who have an abnormal testosterone to estradiol ratio. Here, the anastrozole therapy acts to increase endogenous testosterone levels by inhibiting the synthesis of estrogen [9, 8].
Treatment Outcomes with Anastrozole
Anastrozole has been shown to be very effective in suppressing estrogen production, with studies showing that it can inhibit in vivo aromatization (a step in the chemical reaction in which estrogen is synthesised) by 96.7% and 98.1% respectively when administered as 1 mg or 10 mg daily [10].
In breast cancer treatment, a 58% reduction in incidence of invasive oestrogen receptor-positive breast cancer and a 70% reduction in incidence of ductal carcinoma in situ was recorded in patients receiving anastrozole.
In the treatment of hypogonadal, subfertile men anastrozole improved hormonal profiles and semen parameters, aiding in achieving pregnancy, especially in conjunction with assisted reproductive techniques [9].
Side Effects of Anastrozole
Anastrozole has a good safety profile, however, it has been associated with several side effects. These can include:
- decrease in the bone mineral density in the lumbar spine and hips,
- general increase in bone fractures and joint disorders,
- increase in cholesterol levels [11].
Some more rare side effects can include:
- acne,
- masculinization,
- toxicity to the liver [12],
- adverse effects to the eyes, including severe bilateral papilledema [13],
- musculoskeletal pain [14].
Similarities and Differences Between Tamoxifen and Anastrozole
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Both are effective in treating estrogen receptor-positive tumors or tumors of unknown receptor status. Both drugs have shown to be well-tolerated by patients, with a low rate of withdrawals due to drug-related adverse events [15, 16].
Differences Between Tamoxifen and Anastrozole
Despite their similarities in outcomes and tolerability, there are distinct differences between the two drugs:
- Mode of action - Tamoxifen blocks the estrogen receptor and prevents binding of estrogen, whereas anastrozole inhibits the aromatase enzyme which synthesises estrogen [17, 18].
- Efficacy - Anastrozole has shown superior results in some studies when compared to tamoxifen. For instance, in the Arimidex, Tamoxifen alone or in Combination (ATAC) trial, Anastrozole was significantly more effective than Tamoxifen in disease-free survival in postmenopausal women with early breast cancer, with a 17 and 19% relative risk reduction [19].
- Side effects - Anastrozole has been associated with a significantly lower incidence of side effects to the reproductive system such as endometrial cancer, and cardiovascular system (such as thrombosis). On the other hand, Tamoxifen has been associated with a lower incidence of musculoskeletal disorders and fractures [19].
- Cost - Anastrozole is more expensive than Tamoxifen [18].