This week we’re going to review a controversial topic. Along with this topic comes many associated fears and suspicions. The media has done a great job at creating fears about estrogen. What they gain from it is more attention and more views at the detriment of the female population. My hope is that after reading this post, those feelings will have diminished and hormone therapy can be viewed as a helpful, even positive form of treatment.

Hot flashes. Night sweats. Irritability. Difficulty sleeping. Sound familiar?

The M Word

Let’s start at the beginning. Or rather, should I say, the end. Of your periods that is. What I am referring to, of course, is menopause. Menopause is the time in every woman’s life where her menstrual periods naturally stop. Before they stop all together, however, women go through a phase called perimenopause. This refers to the transition between childbearing years and menopause. During this time, estrogen levels widely fluctuate and gradually decline and often progesterone levels also intermittently stop.

These changing hormone levels occur in response to your body running out of eggs. Every woman is equipped with all the eggs she will ever have by the time she is a developing, 6 month old fetus. This number of eggs can never grow and only declines over time and thus it is genetically determined when you will run out of eggs. Lifestyle choices such as smoking or other inherited autoimmune conditions can cause eggs to die more quickly. Late onset of puberty or contraceptive options that stop ovulation do not preserve your eggs or lengthen your fertile years. 

Menopause occurs when your body runs out of eggs.

Now back to the hormones: essentially, estrogen and progesterone levels drop until they reach their low in menopause. These hormones will never return. In response to these changing hormones, your body goes through a sort of withdrawal and experiences a wide array of symptoms. 15% of women never experience menopause symptoms and another 15% never get over them. Your whole life, you were equipped with plenty of hormones and even relied on them to keep your body functioning, but suddenly these hormones are leaving. 

Symptoms of perimenopause and menopause include hot flashes, night sweats, irritability, mood swings, brain fog, fatigue, difficulty sleeping, headaches and migraines, loss of collagen in skin and therefore increased wrinkles and sagging skin, diminished sexual desire and responsiveness, an painful intercourse. Then there are the symptoms you can’t detect your self such as bone loss, slowing metabolism, and increased risk of heart disease. Some studies have even shown women without estrogen therapy had a higher risk of dementia...just to name a few problems.

A Controversial Topic

"15% of women never experience menopause symptoms, and another 15% never get over them"

If you consult your doctors, it’s likely that you will get mixed opinion. Some will say NEVER go on hormones while others will say YES, definitely go on hormones. Those who say never are often drawing their opinion from a study called the WHI study which is widely popular and was first responsible for releasing concerning information about hormone replacement. The issue with this study is that it was poorly done by a pharmaceutical company which makes Prempro (natural estrogen and synthetic Progestin). They sought to prove that their product improved the health of participants but what they found was in increased the risk of heart disease and stroke as well as the risk for breast cancer.

Let's take a better look into the history of controversial research:

If you look at other research, it can be seen that Hormone Replacement Therapy (HRT) early into menopause in women without any other serious health complications can actually help your health in regards to bone, heart, colon, bladder, and even brain. The risk of breast cancer is not even necessarily increased unless using synthetic Progestin (instead of natural Progesterone). In fact, HRT is approved by the FDA for the treatment of osteoporosis. From an observational perspective, I can testify that patients of mine who began HRT at menopause have better bone density results than those who have never been on HRT. 

The past two decades include a large amount of research that shows a positive association between overall health and HRT. However, a large study called the Women’s Health Initiative (WHI) in 2002 reported an increased incidence of stroke and heart attacks and an increased risk of breast cancer. The study had three research groups: women taking Estrogen and Progestin, women without a uterus taking just Estrogen, and women who took nothing (control group). The majority of women selected for the study were between 60-69 years of age at the start of the trial. The average age of menopause for women is 51. This means that the majority of women in this study were 10+ years into menopause already and the majority had also never used HRT in the past. In the study, women on HRT began to have cardiovascular events (heart attack and stroke) because they were so far into menopause and never exposed to HRT. However, in regards to breast cancer, the group that had the lowest incidence of breast cancer at the end of the trial was not the control as you might expect, but it was actually the group on the estrogen therapy alone. Thus, from this study it can be drawn that the risk of breast cancer may be associated with synthetic Progestin, medroxyprogesterone, instead of Estrogen. 

In our office, nearly all prescribed progesterone is natural Progesterone, Prometrium, rather than the synthetic Progestin, medroxyprogesterone.

The importance of HRT is the timing. If it is given to women early into menopause, there are long term benefits aside from the relief of menopausal symptoms. Some studies even show an increase in overall health and a decrease in mortality (death) in women using HRT near the onset of menopause.

Though these benefits are generally accepted, it is important to understand that HRT should not be used as primary or secondary treatment for cardiovascular disease and should still be mainly used to treat menopausal symptoms or osteoporosis.

The Therapy

Using Hormone Therapy will typically free you of most menopausal symptoms. At our office, we can do blood tests, but we typically cater the hormone therapy to your symptoms and complaints. Numbers can only say so much about how you are feeling and every woman is unique in her needs.

Beginning HRT at the onset of menopause will have positive effects on your body. Estrogen will protect you from osteoporosis by stimulating the cells that build bones. It may protect your heart and colon, though the mechanisms are not exactly understood. Estrogen will also preserve the collagen and elasticity of your skin, helping you retain your youthful complexion and appearance. Along with the preservation of elasticity and collagen comes the benefit of decrease risk of pelvic organ prolapse and improved bladder health. Lastly, HRT may even protect you against dementia.

HRT may be stopped once menopausal symptoms have subsided, however, vaginal moisture and elasticity will likely never return without continued use of a topical vaginal Estrogen. Additionally, when HRT is stopped, bone loss will begin and the cardiovascular benefits will disappear.

Options for HRT

For many women, HRT involves Estrogen plus Progesterone. Estrogen and Progesterone are taken separately, and while there are many options of Estrogen therapy, there are less methods in taking Progesterone.

Progesterone is typically taken as a capsule and is separate from Estrogen therapy. Progesterone is necessary to protect the lining of the uterus by keeping it thin and therefore decreasing the risk of endometrial cancer (uterine cancer). Combination Estrogen and synthetic Progestin pills are available, however Estrogen and natural Progesterone must be taken separately. There is also a combination Estrogen-Progestin patch but because of the synthetic Progestin it contains, I do not typically recommend it in my practice. 

For women without a uterus, Estrogen Therapy alone is suitable.

Estrogen

Systemic

Systemic means that the therapy is done so a detectable level of the hormone circulates through your whole body’s system. In this method, Estrogen circulates through the blood stream, potentially effecting all the cells in the body. The level of Estrogen in the blood tells the brain to stop emitting withdrawal symptoms by decreasing the release of norepinephrine which causes hot flashes, night sweats, irritability, and insomnia. For this reasons, systemic Estrogen is generally required for women with symptoms of hot flashes and night sweats. There are many ways to use systemic Estrogen that will be outline below with their associated positives and negatives:

Transdermal: Patch, Gel, Cream, Spray, Ring

Pros:

• Bypass the liver and therefore minimal affect on increased clot risk
• Continuous absorption and sustained levels of hormone
• Most are plant-based sources (same as bioidentical preparations)
• Consistency in dose
• Convenient; doesn't require a daily action

Cons:

• Less predictable for blood levels due to personal skin differences
• Possible skin irritation to alcohols in gels
• Allergies to adhesive in patch
• Fewer dose options aside from the patch
• Difficult for some people to remember to change their patches

Oral Tablet

Pros:

• Consistently absorbed
• Customized dosing
• Lowers total cholesterol
• Raises good cholesterol
• Consistency in dose
• Comes in many varieties including plant-based, animal-based, and conjugated choices

Cons:

• Goes to the liver first and thus increasing the clot risk
• Hormone levels are not even throughout the day due to quick absorption
• Larger overall amount of hormone
• Inconvenient to take a pill once a day

Bioidentical (Compounded)*

Pros:

• All plant derived (soybean and mexican yam)
• Natural progesterone without peanut oil is available
• No limits or control on doing like with a standard prescription
• May add non-FDA-approved compounds such as testosterone or DHEA
• Comes in essentially any form you can imagine

Cons:

• No quality or oversight
• Possibility of inconsistent dosing

*Bioidentical hormones contain the same risk as any other prescribed HT and is not lower in risk

Local

Local Estrogen is a lower dose applied directly to the vaginal area to treat vaginal dryness and painful intercourse without high circulating systemic levels of estrogen. Topical estrogen comes in five different types.

Cream: Estrace (plant-based) & Premarin (horse-based)

Pros:

• More effective
• Can be directly applied to the areas needed most

Cons:

• Messy

Vaginal Tablet

Pros:

• Not messy

Cons:

• Less effective
• Uncontrolled area of application

Vaginal Ring

Pros:

• Convenient, only changed every 3 months
• Continuous low dose vaginal estrogen
• Very effective

Cons:

• Some people are uncomfortable wearing a ring for 3 months

Osphena: Once a day Selective Estrogen Receptor Modulator (SERM) pill

Pros:

• Estrogen free
• Stimulates the vaginal estrogen receptor to return vaginal moisture

Cons:

• Small percent of women have hot flashes
• VTE (Venous Thromboembolism) risk
• Drug safety in women with a history of breast cancer has not been studied

Progesterone

There are two types of progesterone: natural Progesterone and synthetic Progestin. These typically come in capsules. 

Progesterone creams are generally not effective because unlike Estrogen, Progesterone is a large molecule, and is not easily absorbed through the skin like estrogen. 

Natural Progesterone

Typically produced from the Mexican yam and comes in a capsule suspended in peanut oil. It is also available without peanut oil for those with peanut allergies. Natural Progesterone also comes in a vaginal cream form but is not typically prescribed because it's not very effective. 

Pros (Capsule):

• Consistent dose
• Improves sleep when taken at night
• Calming effect

Cons (Capsule):

• A small percentage of patients experience irritability
• A small percentage of patients experience sleepiness or dizziness during the day
• Not available in a combo pill with Estrogen

Synthetic Progesterone

Pros:

• Powerful Progestin
• Effectively protects the endometrium
• Less expensive than natural Progesterone
• Available in a combo pill with Estrogen

Cons:

• Raises cholesterol
• Increase risk of breast cancer
• Possibility of irritiability or mood swings

Duavee (combined therapy without Progesterone)

Duavee is a relatively new form of combined therapy, free of Progesterone, that contains Estrogen and a Selective Estrogen Receptor Modulator (SERM). It protects the endometrium without using Progesterone for women who cannot tolerate any side effects of Progesterone.

Risks

The true risk of HRT is the risk of blood clots, rather than breast cancer. The risk of blood clot, as many know, is present with any estrogen containing product such as birth control pills. Thus, if you are at risk of blood clots or have cardiovascular disease, Estrogen containing HRT is not a good option. HRT is also not for those with a history of breast cancer, uterine cancer, liver disease, or unexplained uterine bleeding.

The doses of HRT used is still low in relation to the amount of hormone naturally produced by your body during your fertile years. In other words, the amount of HRT you receive in menopause will never exceed the amount you had naturally produced.

The sad part is that medicare does not cover HRT, even with coupons, and some insurances only cover a small amount of the cost of some therapies. A change in the medical care system needs to occur in regards to the hormone therapy for women. The American College of Obstetrics and Gynecology actually recommends HRT for women 65 and older. As it currently stands, many fears are based off controversial science. There is not enough understanding about the needs and concerns of the women affected, or about the specific result of long term natural progesterone and estrogen therapies.

Conclusion

References

Hormone Therapy and Heart Disease. The American College of Obstetrics and Gynecology. Committee 
      Opinion. 2013; 565.
Writing Group for the Women's Health Initiative Investigators. 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.
Stute, P. Is Breast Cancer Risk the Same for All Progesterones? Arch Gynecol Obstet. 2014; 290(2): 207-
      209.
Davey, D.A. Update: estrogen and estrogen plus progestin therapy in the care of women at and after the 
      menopause. Women’s Health (Lond Engl). 2012;8(2):169-189.
Self - Renee Cotter M.D. Practising gynecologist since 1991