Menopause signifies the official end of the menstrual cycle. Typically, this starts in women ages 50 years or older, but it can also occur as early as age 45. This normally occurs when a woman has had at least 12 months without a cycle.
As women age, they lose estrogen production which can lead to notable symptoms of menopause which could be both vasomotor and vaginal. Vasomotor symptoms can include chills, hot flashes, mood changes, night sweats, thinning hair, weight gain, bone-thinning, and dry skin. Vaginal symptoms include vaginal or vulvar dryness, discharge, itching, and dyspareunia (painful intercourse).
Menopause is a natural occurrence in women and although there is no cure for this condition, there are ways to help manage the symptoms.
What are the Different Female Hormones?
To better understand different available therapies and how they work to help manage menopausal symptoms, it is best to first understand some of the different hormones in a woman’s body.
- Estrogen. This is the primary female hormone that contributes most to the growth and health of the female reproductive system. Estrogen stimulates the growth of breast tissue, maintains vaginal blood flow and lubrication, causes lining of the uterus to thicken and helps keep it elastic, and it also helps preserve the integrity of bones.
- Progesterone. This is another female hormone that prepares the lining of the uterus for a fertilized egg.
- Testosterone. Although this is typically considered to be a “male hormone”, it also helps produce estrogen in women. It also contributes to a woman’s libido and helps to maintain bone and muscle mass.
What are the Different Therapies for Menopause Symptoms?
The Endocrine Society defines bioidentical hormones as “compounds that have exactly the same chemical and molecular structure as hormones that are produced in the body.” This can either mean they are non-FDA-approved – meaning they are custom-compounded to match the patient’s needs – or FDA-approved therapies.
The American College of Obstetricians and Gynecologist (ACOG) have guidelines for menopausal management which include medications to help with both vasomotor and vaginal symptoms.
For vasomotor symptoms, they are typically best treated with systemic hormone therapies (HT) and can also be managed with other medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and clonidine. For vaginal symptoms, systemic HT may be an option, but it is often better treated with topical HT. HT may also sometimes be referred to as hormone replacement therapy (HRT).
What are FDA-Approved Therapies for Systemic HT and Vaginal HT?
FDA-approved HT therapies are made by a pharmaceutical company (manufacturer). Systemic HTs have been shown to be effective in treating vasomotor symptoms of menopause. Typically, they are estrogen-based, but they can also be combined with progestin (synthetic progesterone). Many of these medications come in forms of patches, creams, rings, or tablets.
Estrogen medications most commonly come in estradiol forms or as conjugated estrogens. Products that contain estrogen will be either synthetic conjugated estrogens – natural, nonhuman conjugated estrogens (derived from urine of pregnant horses) – or plant-derived bioidentical estrogens. Vaginal HTs are mainly estrogen or estrogen/progestin-based and they are inserted in the vagina in the forms of creams or suppositories.
Table 1. FDA-Approved Estrogen-Based and Estrogen/Progestin Formulations
| Brand | Generic | Route available | Estrogen only? |
| Climara | Estradiol | Transdermal | Yes |
| Estrace | Micronized estradiol-17? | Oral/Vaginal cream | Yes |
| Estring | Micronized estradiol-17? | Vaginal ring | Yes |
| Femring | Estradiol acetate | Vaginal ring | Yes |
| Premarin | Conjugated estrogen | Oral/Vaginal cream | Yes |
| Vagifem | Estradiol | Vaginal tablet | Yes |
| Premphase | Conjugated equine estrogens and medroxyprogesterone acetate | Oral | No |
| Prempro | Conjugated equine estrogens and medroxyprogesterone acetate | Oral | No |
| Activella | Estradiol-17? and norethindrone acetate | Oral | No |
FDA-approved progestin-based medications can be used for hormone therapy as well. There are vaginal gels available, but oral formulations are most common.
- Oral formulations
- Medroxyprogesterone
- Norethindrone
- Progesterone capsules
FAST FACT: Manufactured progesterone capsules are made in peanut oil to help the body better absorb this medication. It is important to note if any peanut allergies are present before taking this form of progesterone.
What Are the Different Compounded Hormone Therapies?
Although manufactured HT medications are available, many times people will get compounded HT. Compounded HT therapies are not FDA-approved but they are commonly used in practice.
Compounded hormones contain mainly estrogen and progesterone derivatives. However, testosterone, dehydroepiandrosterone (DHEA), and pregnenolone hormones can also be added. There are three main estrogens that can be used in a compound: 17-? estradiol, estriol and estrone.
17-? estradiol is the strongest and predominant form of estrogen in the body, while estriol is the weakest of the three estrogens and does not last long in the body. There are certain hormonal therapies where only estriol is used to help with the menopausal symptoms. Because of certain weak chemical interactions, estriol might be a safer option than its stronger counterparts, estradiol and estrone. This review examined different studies using estriol in different dosages to assess the safety and efficacy of estriol.
Progesterone is mainly used to prevent the development of endometrial hyperplasia, a condition that occurs when the lining of the uterus becomes too thick due to excess amounts of estrogen. Therefore, it is important for many patients to also have progesterone included with any estrogen-based hormone therapy if their uterus is still intact.
What Are the Risks Associated with HT?
There are certain risks associated with taking hormonal menopausal therapies. The most pertinent being cancer and thromboembolic risks:
- Increased risk of cancer. Estrogen therapies have been more associated with development of endometrial cancers. That is why it is critical for people to be given progesterone along with estrogen to reduce cancer risk if their uterus is intact.
- Increased risk of venous thromboembolic disease. Estrogen based therapies can increase the risk of clotting conditions such as strokes (clotting in the brain), pulmonary embolism (clotting in the lungs) and deep venous thrombosis (clotting in the legs). If the person smokes, it is important for them to quit because this further increases their risk of experiencing a clot while on estrogen therapy.
What Are Contraindications for HT?
Contraindications for use of menopausal hormone therapy include:
- Active liver disease
- Active or history of arterial or venous thromboembolic diseases (i.e. angina, heart attacks, pulmonary embolism, deep venous thrombosis)
- Current, past, or suspected breast cancer
- Known allergies to any of the active or inactive ingredients
- Known or suspected estrogen-sensitive malignant conditions
- Undiagnosed genital bleeding
- Untreated endometrial hyperplasia
- Untreated hypertension (high blood pressure)
What are the Benefits and Risks of FDA-Approved vs. Non-FDA-Approved HT?
There is a long-standing debate over which is better between FDA-approved HT or non-FDA approved compounded HTs. So, some benefits and risks for both sides are discussed in this section.
- FDA-approved HTs are carefully controlled and regulated formulations, especially relating to vaginal preparations. They are also manufactured and go through strict standards of how they are produced. A main drawback is that they are not produced to personalize to a person’s hormonal needs and a person may be allergic to any inactive ingredient the product may have.
- Non-FDA-approved compounded HTs provide individualization to the person and their needs, and different routes of administration can be incorporated that manufactured products cannot provide. However, large-scale controlled studies using compounded HTs have not been conducted.
What are Some Key Takeaways if a Person Wants to Start HT or if a Provider Wants to Prescribe HT?
If you are interested in receiving hormonal therapy, these tips may help:
- Ensure you have stopped smoking as estrogen therapy will increase your chances of developing a major clot that can either go into your lungs, legs, or brain.
- Talk to your healthcare provider about the types of symptoms you are experiencing as this will help steer them to the right treatment plan for you.
- Ensure you are getting seen by your healthcare provider at least once every year for your blood pressure, lipid profile (i.e.cholesterol), weight, mammogram (if you are 40 or older), and pap smear.
For physicians wanting to prescribe hormonal therapy:
- Ensure the individual is not contraindicated for HT.
- If the uterus is intact, prescribe progesterone with any estrogen therapy to prevent the occurrence of endometrial hyperplasia.
- Assess the symptoms of menopause that the person is experiencing to help direct the erson to a more personalized treatment plan. If the person experiences more vaginal symptoms, then a hormone vaginal cream may be warranted over oral treatment. However, if a person has more vasomotor symptoms or both, then an oral or transdermal treatment may be needed.
With many different treatment options available for helping manage menopausal symptoms, there is a way to get through menopause without having to experience these negative effects.
References:
- Croke, L. M. (2014, September 1). ACOG Releases Clinical Guidelines on Management of Menopausal Symptoms. American Family Physician. https://www.aafp.org/afp/2014/0901/p338.html.
- Facts about Menopausal Hormone Therapy. National Institute of Health. https://www.nhlbi.nih.gov/files/docs/pht_facts.pdf
- Head KA. Estriol: safety and efficacy. Altern Med Rev. 1998;3(2):101-113.
- Randel, A. (2012, November 1). AACE Releases Guidelines for Menopausal Hormone Therapy. American Family Physician. https://www.aafp.org/afp/2012/1101/p864.html. q
- Files JA, Ko MG, Pruthi S. Bioidentical hormone therapy. Mayo Clin Proc. 2011;86(7):673-680. doi:10.4065/mcp.2010.0714
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