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Endocrine Therapy for Premenopausal Women

Premenopausal women with breast cancers that express the estrogen and/or progesterone receptor (ER and/or PR-positive) will often be encouraged to take tamoxifen for five years. This drug impacts the effects of estrogen in cancer cells and helps reduce the risk that the breast cancer will recur in women of any age by almost 50 percent.

Tamoxifen can also help reduce the risk of developing a new breast cancer in the unaffected breast. In some cases, women who are younger than 35-40 may also be considered for combined endocrine therapy with medications that temporarily stop ovarian function.

NOTE: Many women stop menstruating after receiving chemotherapy, often for several months or even a few years. It is possible that these women could still have functioning ovaries and premenopausal hormonal levels despite the absence of their menstrual periods. Also, ovarian function could still return unexpectedly. That said, women who are premenopausal, regardless of whether they experience temporary menopause because of treatments, should not be prescribed aromatase inhibitors (unless they are participating in specific clinical research studies). Aromatase inhibitors are typically reserved for postmenopausal women with breast cancer.

Side effects of tamoxifen

The side effects of tamoxifen are generally mild and decrease with time. They include:

  • Hot flashes
  • Vaginal discharge
  • Menstrual irregularity
  • Hair loss
  • Skin changes
  • Decreased interest in sexual activity
  • Fertility issues
  • Memory loss
  • Fatigue
  • Joint pain
  • Headaches
  • Insomnia or trouble sleeping
  • Increased sweating
  • Nausea
  • Weight changes
  • Mood swings

Some side effects can be alleviated through symptom management and other lifestyle changes

Risk Factors

Serious complications with tamoxifen are rare, especially in women younger than age 50, and may include blood clots (deep venous thrombosis or pulmonary embolism) or uterine (endometrial) cancer.

Ovarian Suppression or Ablation

For premenopausal women with estrogen receptor-positive breast tumors, ovarian ablation or suppression (stopping ovary function) may be an option. Since a premenopausal woman’s ovaries are the main source of estrogen production, temporarily or permanently shutting off their function has been shown to be effective (when used alone) in reducing the chances of a breast cancer recurrence. Studies are now confirming their usefulness when given with tamoxifen instead of chemotherapy or after chemotherapy. This is called ovarian ablation or suppression and can be done through surgery (permanently) or monthly hormonal injections (temporarily). The injection of medication will prevent you from ovulating or menstruating and will put you in temporary menopause. Surgery will prevent you from having to undergo monthly injections, but will put you in irreversible menopause. You should speak to your doctor regarding any plans to conceive children so that together you can decide which option is best for you and your family.

Ovarian Ablation

A bilateral oophorectomy (or ovarian ablation) is the surgical removal of your ovaries. This procedure is sometimes recommended if you have been identified as carrying a BRCA1 or BRCA2 genetic mutation and have an increased risk of developing ovarian cancer.  The surgical removal of your ovaries will reduce circulating estrogens in your body down to postmenopausal levels. This surgery is permanent and cannot be undone. For premenopausal women, an oophorectomy will prevent you from conceiving children and will cause permanent menopause.

Ovarian Suppression

Ovary suppression can be achieved by hormonal drug injections called gonadotropin-releasing hormone (LH-RH or GnRH) agonist. This works by temporarily suppressing ovulation and, as a result, limiting the amount of estrogen circulating in your body. Estrogen levels usually are reduced to postmenopausal levels within two weeks. Treatment is generally administered by monthly injections. Although you will be in a temporary menopause while taking this drug, this is generally reversible and menstruation often begins shortly after treatment stops. This is not a fail-proof birth control method so you should use a non-hormonal form of contraception too, like an IUD or barrier methods such as condoms or a diaphragm. Side effects are similar to menopausal symptoms and include decreased sex drive, hot flashes, weight gain and bone pain.

To maximize effectiveness, ovarian suppression drugs and tamoxifen are prescribed together.

Drug interactions


It is estimated that as many as 30 percent of all breast cancer patients in the United States are prescribed an antidepressant at sometime during their treatment. Some antidepressants interfere with how tamoxifen works and therefore should be avoided.

The following antidepressants are expected to interfere with tamoxifen:

Paxil® (paroxetine)
Prozac® (fluoxetine)
Wellbutrin® (bupropion)

The following drugs are believed to have a moderate interference with tamoxifen:

Zoloft® (sertraline)
Cymbalta® (duloxetine)

The following antidepressants have been shown to be less likely or unlikely to interfere with tamoxifen:

Effexor® (venlafaxine)
Lexapro® (escitalopram)
Celexa® (citalopram)

Other Medications

There are other drugs that are not classified as antidepressants but are believed to interfere with tamoxifen and should be avoided. These include:

Cardioquin® (quinidine)
Benadryl® (diphenhydramine)
Mellaril® (thioridazine)
Cordarone® (amiodarone)
Tagamet® (cimetidine)