The A to Z of endocrine therapy

Dr Inge Kriel fills in the blanks of endocrine therapy.

If you’re a patient with oestrogen-receptor positive breast cancer, then  you may feel overwhelmed by all the different endocrine treatments out there.

In addition, due to time constraints, oncologists may not necessarily explain in detail how these therapies work and why they are so important.

Firstly, why is endocrine therapy important?  

It significantly reduces the risk of breast cancer recurrence. The risk reduction is so significant, that recent studies have advised prolongation of therapy from five years up to 10 years in selected patients. Studies have shown that the benefits outweigh the potential risks of long-term use.

Types of endocrine therapies

The main groups of endocrine therapies available include:

1) Aromatase Inhibitors (AIs)

Non steroidal (reversible) AI

  • Anastrozole (Arimidex/Stradexa)
  • Letrozole (Femara)

Aromatase inactivator

  • Steroidal (irreversible)
  •                    Exemestane (Aromasin)

What do AIs do? The aromatase inhibitors/inactivators block the conversion of androgens to oestrogen (by blocking the function of a hormone called aromatase).

2) Selective oestrogen receptor modulators (SERMs)

  • Tamoxifen (also known as Kessar, Neophedan, Nolvadex, Tamoplex)
  • Toremifene (Fareston)
  • Raloxifene (Evista)

What do SERMs do? The selective oestrogen receptor modulators block the oestrogen receptors in breast tissue, but may activate oestrogen receptors in bone/liver/uterine tissue – hence the word selective.

3) GnRH agonists

Goserelin (Zoladex)

What does GnRH agonists do?

This is an injection given every three months. It “shuts the factory down” – in other words it stops the ovaries from producing oestrogen.

This is typically given to patients who were pre-menopausal at the time of their breast cancer diagnosis. While chemotherapy may put some patients into permanent menopause, other patients may recover function of their ovaries after chemo is completed, and therefore resume producing oestrogen.

A blood test called a post-menopausal screen will help to identify those patients whose ovaries have “switched back on again”

This is usually given in conjunction with tamoxifen, for at least two years (duration dependent on your oncologist).

Side effects

The AIs are especially notorious for causing joint aches and bone loss (osteopaenia). This can be managed through calcium and vitamin D supplementation (and bisphosphonate therapy in severe cases), chondroitin/collagen supplementation, duloxetine (an anti-depressant that has recently been shown to improve aromatase-inhibitor associated joint aches), and most importantly exercise (especially weight-bearing exercise).

Tamoxifen may have the following side-effects:


1) Blood clots (very rarely encountered in the absence of other risk factors).

2) Thickening of the lining of the womb which may lead to endometrial cancer if not addressed. This can be assessed via ultrasound measurement by a gynaecologist.

Generally, if greater than 8mm a dilatation and curettage can be done to remove the excess tissue.

According to the American College of Obstetricians and Gynecologists, the small risk of endometrial cancer amongst patients on tamoxifen is significantly outweighed by the benefit of tamoxifen in terms of increased breast cancer survival rates.

Common: Generalised joint aches, muscle cramps, hot flushes, dry skin, vaginal dryness, and mood swings (Hello menopause!)


All of these side effects can be managed by your oncology care physician. Report all side-effects; you don’t have to suffer in silence. Effective treatments are available to alleviate side effects.

Sometimes patients may react too severely to certain endocrine agents, or the endocrine agent may stop doing its job as well as previously, and then it may be necessary to switch to a different generic within the same group, or even another endocrine agent altogether.  There is no one size fits all. Sometimes it’s a process of trial and error to find the best fit for you. Hang in there – you will find the right agent to give you the best protection against recurrence while limiting the side-effects experienced.

Dr Inge Kriel is an oncology care physician practicing at Netcare Milpark Hospital.


Dr Inge Kriel is an oncology care physician practicing at Netcare Milpark Hospital.