Postmenopausal HRT

Postmenopausal Hormone Replacement Therapy


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Hormone replacement therapy (HRT) in postmenopausal women has been more controversial since the publication of the Women’s Health Initiative (WHI) (see findings in 2003. Many women have stopped taking estrogen on their own, or have been told to do so by their healthcare provider, and now those women are having hot flashes or other sequelae of menopause. This has caused a lot of discomfort for patients and in many, if not most cases is an over-reaction to the findings of the WHI.
In looking at the actual numbers from the study, the risk to patients taking estrogen plus progestin (HRT) is really low in comparison to placebo. For every 10,000 women taking estrogen plus progestin pills:

38 developed breast cancer each year compared to 30 breast cancers for every 10,000 women taking placebo pills each year.
37 had a heart attack compared to 30 out of every 10,000 women taking placebo pills.
29 had a stroke each year, compared to 21 out of every 10,000 women taking placebo pills.
34 had blood clots in the lungs or legs, compared to 16 women out of every 10,000 women taking placebo pills.

For patients who are having significant hot flashes, trouble sleeping, mood changes and loss of sex drive, the benefits of HRT in terms of quality of life are substantial and most patients will opt for HRT after an objective discussion of risk. The FDA and most other medical groups recommend using the lowest effective HRT dose for the shortest possible time, but how can that be done in practice?

When starting a patient on HRT, I usually choose a dose in the range of 1mg estradiol or 0.625mg of conjugated estrogen. I like using Activella (1mg estradiol + 0.5mg norethindrone) or Prempro (0.625mg conjugated estrogen + 2.5mg medroxyprogesterone). Activella is available as a generic and comes in a lower dose (0.5mg estradiol + 0.1mg norethindrone); Prempro is available in several doses but not as a generic.

For patients without a uterus, estrogen alone (ERT) can be used for menopausal symptoms. For ERT, the WHI showed an increase in thromboembolic disease and stroke, but not for breast cancer or heart disease. We are of course, still concerned about long-term use of these drugs and so the same principle applies, that is, to use the smallest effective dose for the shortest possible time. Estradiol is easy to use and available as a generic in several different doses; 1 mg is a good starting dose.

I see my patients on HRT or ERT yearly, and I ask if they have had any hot flashes or night sweats. Usually they have missed a few doses of meds here and there throughout the year. If they don’t seem to have any problems when they miss a dose or two, then that is a good time to consider decreasing the dose. Once a patient is on the lowest oral dose (0.5mg estradiol or 0.3mg conjugated estrogen), then consideration can be given to stopping the medication once no (or very few) hot flashes are reported. Once a patient is off her ERT or HRT, she may experience more vaginal dryness and estrogen cream or vaginal estrogen tablets can be considered.

I don’t recommend phytoestrogen (plant estrogens like black cohosh or red clover), progesterone cream or evening primrose oil. There is little scientific evidence behind these agents and they may confer some risk. Why choose these agents, with essentially unknown or uncertain benefit and risk, when we have pharmaceutical grade products that work, and about which the benefit and risk is better quantified?

There are some special situations that should be mentioned.

If a patient has significant vaginal dryness symptoms, along with hot flashes or other systemic symptoms, Femring can be considered.  This is a very convenient vaginal ring that is flexible. The patient generally cannot even feel it and it can be left in all the time. Femring comes in two doses, 0.05mg and 0.1mg estradiol, and lasts for 3 months.

For breast cancer survivors, who have no clinical evidence of disease, the Estring is a consideration. This is a vaginal ring with extremely low dose, effective for vaginal dryness in these patients. Most oncologists feel that this is a safe product for breast cancer patients because of the low dose with minimal or no absorption (vaginal estrogen cream would not be a safe choice in such patients).

If a patient does not tolerate oral HRT or ERT well, then a transdermal patch can be used. There is a once a week ERT patch called Climara that is available in several doses, and available as a generic. The 0.05mg/24hr dose is a good place to start. This patch is changed weekly. Vivelle dot is a small, easily applied patch that is changed twice a week.
There are HRT patches as well. Combipatch is available in 2 doses (changed twice a week), and Climara Pro is available in 1 dose, changed weekly.

Finally, some patients have vaginal spotting or bleeding on HRT. If the bleeding is so light that protection is not even needed, I just watch to see if it increases. Bleeding that requires protection demands investigation, usually in the form of an endometrial biopsy. Once a “pattern” of bleeding is established, then it does not have to be investigated again unless or until that pattern changes.

We should not be afraid to give estrogen to patients who need it. It is good to review the risks of ERT and HRT with each patient being given these medications. If the patient then hears something about the risks of estrogen, she will be better informed. We need to decide in each case if the risks of estrogen use are outweighed by the benefits, which may include better sleep, better quality of life, better sexual and bone health.


Casey Younkin, MD
Southern Illinois University School of Medicine
Springfield, Illinois

Published on March 19, 2013

Dr. Casey Younkin is an associate professor on the faculty at Southern Illinois University School of Medicine in Springfield, IL. He has been interested in bone health for many years and is a member of ISCD (International Society of Clinical Densitometry) and ASBMR (American Society for Bone and Mineral Research). His goal is to see every patient with a fragility fracture evaluated and potentially treated, to prevent the next fracture from occurring.



  1. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3): 321–333.
  2. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49-57.