Hormone Replacement Therapy
In hormone replacement therapy, women supplement their natural estrogen production with external sources of the hormone. Because menopause symptoms are directly caused by decreases in estrogen and progesterone, external supplementation is extremely effective in decreasing the severity of symptoms such as hot flashes, vaginal dryness, bone loss, and mood swings.
hormonesWhile hormone replacement therapy is effective in reducing menopausal symptoms, there is a chance your symptoms will come back once you stop the therapy.
The decision to use hormone replacement therapy is complex and depends on your unique situation and circumstance. HRT has several possible side effects and it is recommended that the lowest effective dosage for the shortest time be used.
Women who experience premature or early menopause may be stronger candidates for hormone replacement therapy. Young women are also more likely to use full-dose estrogen dosages, as low-dose estrogen therapy at a young age does not maintain bone density. Some women with induced menopause due to cancer, hormonal therapy may not be appropriate.
Estrogen and progesterone come in a variety of pills, patches, gels, creams, and emulsions. In early perimenopause, some doctors may prescribe birth control pills (which contain estrogen) to help with irregular periods. As you get closer to menopause and start to experience other side effects such as hot flashes or vaginal dryness, your doctor may prescribe estrogen and/or progesterone directly.
Indications
Hormone replacement therapy can help with menopause symptoms by:
Reducing hot flashes
Treating vaginal dryness
Slowing bone loss
Decreasing mood swings and depression
Improving sleep
Contradictions
Women should not take hormone replacement therapy for menopause if:
Think they are pregnant
Have problems with vaginal bleeding
Have had certain kinds of cancers (such as breast and uterine cancer)
Have had a stroke or heart attack
Have had blood clots
Have liver disease
Hormone Replacement Therapy Products
Finding the right regimen of estrogen type, form, and dosage may require time and patience. There are two types of pure estrogen dosage forms (systemic and local), a customized compound forms created by your pharmacist, and combination estrogen and progestrogen produts.
Estrogen Products Used to Treat Menopause in the US and Canada
Estrogen Type
Oral Tablet
Product Name
Skin Patch/Gel
Product Name
Vaginal Form
Product Name
conjugated equine estrogens
Premarin
N/A
Premarin Vaginal Cream
synthetic conjugated estrogens
Cenestin
Congest**
CES
PMS-conjugated
N/A
N/A
esterified estrogens
Menest
Neo-Estrone
N/A
Neo-Estrone Vaginal Cream**
estropipate (Piperazine estrone sulfate)
Ortho-Est
Ogen
N/A
Ogen Vaginal Cream
17beta-estradiol
Estrace
Alora
Climara
Esclim
Estraderm
Estradot**
Estrogel**
Oesclim**
Vivelle
Vivelle-Dot
Estrace Vaginal Cream
Estring Vaginal Ring
ethinyl estrodiol
Estinyl
N/A
N/A
estradiol hemihydrate
N/A
N/A
Vagifem Vaginal Tablet
estradiol acetate
N/A
N/A
Femring Vaginal Ring
Systemic Dosage Form
In systemic dosage form, estrogen circulates throughout the entire body and affects many tissues. Systemic dosage forms include oral pills, skin patches / gels, and injections. The full range of benefits and risks are associated with this form of hormone replacement therapy. Estrogen injections are not recommended for menopause treatment as direct injection does not supply a stable long lasting level of hormones and instead aggravates the hormonal fluctuations experienced in perimenopause. Additionally, women who have not had a hysterectomy (i.e. still have a uterus) should use a combination of estrogen and progestogen to protect against the risk of endometrial cancer.
Local Dosage Form
In local dosage form, the active hormone(s) only affect the immediate localized area. The vast majority of vaginal estrogen products are considered local. These would include vaginal creams, rings, and vaginal tablets. Local dosage forms are most commonly used to treat moderate to severe vaginal dryness and atrophy. Only a small amount of the hormone estrogen circulates through the body and thus it is not appropriate for treating other symptoms of menopause such as hot flashes and osteoporosis. One exception to this rule is the new estradiol acetate vaginal ring (Femring). The Femring does deliver a systemic dosage of estrogen so it can address hot flashes. As in systemic dosage forms, it is recommended that women with a uterus add progestogen to routine when using Femring and other high dosage local forms so as to mitigate the risk of endometrial cancer.
Customized Forms
In addition to the standard estrogen formulations listed, your doctor may prescribe a “compounded” dosage form that is custom made by your pharmacist. These compounded forms are customized, both in the active ingredient(s) used and in the physical form. Examples includes various capsules, skin creams, gels, subdermal implants, sublingual tablets, rectal suppositories, and nasal sprays. Some types of estrogen are only available as a compound. For example, estriol, a weak estrogen with 5-10% the strength of 17beta-estradiol is typically compounded in an oral mixture with three other estrogens (80% estriol, 10% estrone, and 10% 17beta-estradiol). This is known ass Tri-est.
Progestogen Combinations
Progestogen is another female hormone is commonly combined with estrogen to treat perimenopause symptoms such as hot flashes. It’s primary benefit however is to protect against the risk of uterine cancer. Using a pure estrogen therapy alone for 5 or more years increases the risk for uterine cancer by 3 times or more. Adding progestogen helps mitigate this risk by preventing the endometrium from thickening.
Progestogen Type
Formulation
Product Name
Oral Tablet
(Progestin)
medroxyprogesterone acetate (MPA)
Provera
multiple generics
norethindrone (norethistreone)
Micronor
Nor-QD
norethindrone acetate
Aygestin
norgestrel
Ovrette
Intrauterine Device
(UID) (Progestin)
levonorgestrel
Mirena
Oral Capsule
(Progesterone)
micronized progesterone USP (in peanut oil)
Prometrium
Vaginal Gel
(Progesterone)
progesterone
Prochieve 4%
Combined estrogen and progestogen therapy is what most people call “Hormone Replacement Therapy”, but the preferred technical term is estrogen-progestogen therapy (EPT). EPT is also used in birth control pills, but at a dosage level that is much higher than forms used primarily for menopause treatment.
Like estrogen, there are many different forms of progestogen and, additionally, your pharmacist is also able to create customized compounded formulations as well.
Estrogen-Progestogen Products Used to Treat Menopause
Regimen
Formulation
Product Name
Continuous-Cyclic
(Oral Tablet)
conjugated equine estrogens
medroxyprogesterone acetate
Prempahse
Continuous-Combined
(Oral Tablet)
conjugated equine estrogens
medroxyprogesterone acetate
Premrpo
Premplus
ethinyl estradiol
norethindrone acetate
Femhrt
17beta-estrodiol
norethindrone acetate
Acitvella
Intermittent-Combined
(Oral Tablet)
17beta-estrodiol
norgestimate
Prefest
Continuous-Combined
(Skin Patch)
17beta-estrodiol
norethindrone acetate
CombiPatch
Esalis
Continuous-Cyclic
(Skin Patch)
17beta-estrodiol
norethindrone acetate
Estalis Sequi
Estracomb
Estrogen-Progestogen Therapy Regimens
Various schedules and protocols can be followed. Each woman should work with her healthcare professional in determining the best schedule. The most commonly used regimens are listed below:
Cyclic HRT (EPT)
Estrogen is taken for 25 days each month
Progestogen is taken in addition to the estrogen for the last 10 – 14 days
No hormones are taken for the last 3 to 6 days of the month
This type of regimen is becoming less popular because of the uterine bleeding that occurs at the end of the progestogen cycle (withdrawal bleeding). Additionally, hot flashes are possible during the estrogen free period.
Continuous-Cyclic HRT (EPT)
Estrogen is taken every day during the month
Progestogen is taken in addition to the estrogen for 10 – 14 days each month
Like cyclic HRT, uterine bleeding occurs in approximately 80% of women when the progestogen cycle ends, but in many women, the incidences of bleeding gradually decline and stop over several months.
Continuous-Combined HRT (EPT)
Estrogen and Progestogen are taken everyday.
Less uterine bleeding is experienced with this regimen. Nearly 90% of women have uterine bleeding stop by 1 year into the therapy.
Intermittent-Combined HRT (EPT)
Estrogen is taken every day during the month
Progestogen is taken intermittently in a 3-day on, 3-day off cycle
This is among the newest regimens. Bleeding and endometrial cancer protection are similar to that of the continuous-combined regimen.
Side Effects
Hormone replacement therapy may have the following side effects:
Uterine Bleeding
Breast tenderness or enlargement
Nausea
Bloating and fluid retention
Headaches
Hair loss
Mood Changes
Additionally, for certain women, hormone therapy may increase the risk of blood clots, heart attacks, strokes, breast cancer, and gall bladder disease.
Recent Research and HRT Risks
Hormone replacement therapy has been the main treatment for menopause symptoms for over 60 years. However, HRT has become controversial as of late. Results from several recent long-term NIH studies showed that a certain combination of estrogen and progesterone slightly increased the risk of heart attack and stroke. This came as a surprise as many researches had theorized that estrogen supplementation would help prevent heart attacks by raising levels of good HDL cholesterol and lower levels of bad LDL cholesterol.
The results of these studies have called into question the use of hormone replacement therapy. However, many experts have correctly pointed out that the specific conclusion of the study was that hormone therapy should be used for disease prevention. The study did not address the appropriateness of using hormone therapy to menopause symptoms.
What’s the bottom line? Hormone replacement therapy is still an effective treatment for menopause, but you and your doctor should carefully examine the benefits and risks and make an informed decision.
Pros and Cons of HRT
Pros Cons
Reduces the risk of osteoporosis Potential side effects like bloating or breast tenderness
Relieves hot flashes and night sweats Estrogen alone modestly increases risk of endometrial cancer
Relieves vagianl dryness Increases risk of blood clots
Improves cholesterol levels May initially increase risk of heart attacks and strokes
May reduce risk of heart disease May initially increase risk of breast cancer with extended use
May improve mood and well-being Pill form may contribute to gallbladder disease
May prevent decline of mental abilities
birth control pills