Hormone Replacement Options in Menopause and Perimenopause

progesterone cream jar

By Lorraine Maita, MD, Summit, NJ
Forever Health Network Practitioner

If you are experiencing symptoms of menopause such as hot flashes, night sweats, bone loss, dry eyes, skin, and vagina, your level of hormones like estrogen and progesterone may be low. If you are perimenopausal and are experiencing anxiety, irritability, insomnia, fluid retention, breast tenderness, and weight gain, you might be suffering from estrogen dominance, which often results from low progesterone as well. In either case, you might be contemplating some hormone replacement options and want to know the pros and cons.

With hormone replacement therapy (HRT), important consideration must be given to the route of administration and the form or type of hormone (synthetic or bioidentical) used.

Hormone Replacement Options by Route of Administration

Whether by pill, patch, cream or pellet, the way you take a hormone can affect its absorption and blood levels in your body, as well as present different side effects:

  • Oral estrogen has been found to inflame the liver, increase the risk of gallstones, and encourage the formation of blood clots. The clots that form on plaque in arteries can break off and travel to internal organs, increasing the risk of heart attack and stroke. (This is known as VTE or venous thromboembolism.)2 The liver also increases the level of a protein called sex hormone binding globulin (SHBG) that binds hormones like estrogen and testosterone and makes them less available to the tissues. Only free, unbound hormone can have an effect.
  • Transdermal estrogen involves applying a hormone-infused patch to the skin. For those worried about side effects, it may be a better hormone replacement option since the hormone becomes available to the tissues at a lower dose.2,3,4,5
  • Topical progesterone is available in cream or gel form applied to the skin. However, menopausal women suffering from anxiety and insomnia may receive a greater benefit from taking progesterone orally. The liver metabolizes oral progesterone to produce allopregnanolone, which acts on the GABA receptors in the brain to calm the nervous system. That calming effect could encourage better sleep.

Hormone Replacement Options by Form for Women

There is and always will be a debate regarding the safety and efficacy of bioidentical hormones and synthetic hormones, especially for women who are concerned about the risk of heart disease and breast cancer.1

Many large-scale studies have been conducted on synthetic hormones and some on bioidentical hormones. Back in 1991, the Women’s Health Initiative (WHI) was a major, federally funded study that used high-dose, oral, synthetic hormones (the most common replacement option available at that time) on women whose average age was 63 and were roughly 10 years beyond menopause. The results showed that the risk of stroke and heart attack was higher in women who took those oral hormones. Those findings scared many a doctor from prescribing hormones and many patients from taking them.

In recent years, hormone replacement research on different routes of administration and forms such as synthetic versus bioidentical and topical versus oral has yielded a variety of results. However, many studies seem to share the conclusion that bioidentical hormones, specifically transdermal estrogen and oral natural progesterone, may be better hormone replacement options.

  • In a 2009 review of the published literature, Kenneth Holtorf, M.D., concluded: “Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.”1
  • The author of a 2013 study on HRT optimization noted that a combination of bioidentical hormones (with estrogen given topically and progesterone given orally) may be more beneficial hormone replacement options. Transdermal estrogen appeared to decrease the risk of clots, embolism, stroke, and gallbladder disease. Bioidentical progesterone had positive effects on decreasing blood pressure, clots and embolism, and even breast cancer.2
  • In 2012, the author of a review concluded: “The use of transdermal estradiol [bioidentical estrogen] and micronized progesterone [natural bioidentical progesterone] could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis [inflammation of the gallbladder], and possibly even breast cancer associated with oral HRT use.” The author also cited positive statements about the same type of HRT in the guidelines from four menopause societies.3
  • A paper published in 2008 reviewing studies on the safety of transdermal estrogen plus progesterone determined that the risk of blood clots and liver and gallbladder disease with transdermal estrogen was negligible and that natural progesterone had a favorable effect on the blood vessels and brain and may even confer less or no risk of breast cancer.4
  • In 2012, researcher A.O. Mueck cited experimental and clinical data in a review that found the combination of transdermal bioidentical estradiol and micronized progesterone protected the heart and decreased the risk of new-onset diabetes. It was recommended as a better hormone replacement option.5
  • A 1996 review of studies concluded that when it comes to the risk of breast cancer in healthy postmenopausal women, the benefits associated with estrogen replacement therapy/hormone replacement therapy outweigh the risks.6

Although the news media often focuses on the negative, sensational studies that are still using the same study population from the Women’s Health Initiative, more and better hormone replacement options and studies that evaluated their safety exist now. By reading some of the other studies that used more updated treatment regimens, you can formulate your own opinion.

Since there is a lot of contradiction in the literature and a lot of misinformation in the media, when you begin thinking about hormone replacement options, it is important to have a discussion with a functional medicine doctor familiar with many forms of hormone replacement therapy as well as how your body metabolizes them. Everyone metabolizes them differently. A good physician will take into account your individual risk factors, symptoms, levels, and other factors and help you determine what, if any, hormone replacement options would be most appropriate for you. Educate yourself and don’t allow headlines or one doctor’s opinions to sway you. Make your own decision. There is no need to suffer. If you have symptoms, consider hormone replacement options. 

To learn more about Dr. Lorraine Maita in Summit, NJ - visit her Forever Health profile.


  1. Postgrad Med. 2009 Jan;121(1):73-85.
  2. Climacteric. 2013 Aug;16 Suppl 1:44-53.
  3. Climacteric. 2012 Apr;15 Suppl 1:3-10.
  4. Maturitas. 2008 Jul-Aug;60(3-4):185-20.
  5. Climacteric. 2012 Apr;15 Suppl 1:11-7.
  6. J Clin Oncol. 1996 Mar;14(3):997-1006.

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