Navigating Female Hormones: A Pharmacist's Guide to HRT

Ashley Firm, PharmD; Caitlin Bertrand, PharmD; Cara Dantzler, PharmD


US Pharmacist. 2015;40(9):33-37. 

In This Article

Hormone Basics

HRT is a topic most women will discuss with their friends, physician, and possibly their pharmacist as they approach menopause. With so many options available, including rings, patches, creams, tablets, and capsules, how does the pharmacist conduct this challenging conversation? Most pharmacists can clearly and concisely explain diabetes, hypertension, and asthma, but what about the balance between estrogen and progesterone? How does the pharmacist explain to a patient why her doctor is recommending testosterone replacement, or why the HRT that is effective for her friend may not be the best option for her?

HRT was developed to reduce (and, hopefully, eliminate) the undesirable symptoms of menopause. Menopausal symptoms are experienced when the hormones typically produced by the ovaries during the reproductive years begin to decline. Symptoms of hormone imbalance include weight gain, hot flashes, dry skin, vaginal dryness, headaches, irritability, mood swings, insomnia, decreased sex drive, and fatigue. Symptoms of specific hormone excesses and deficiencies are listed in Table 1. By supplementing or replacing these hormones with manufactured or specially compounded HRT, many women are able to correct the hormone imbalances contributing to menopausal symptoms. The first step to understanding hormone imbalances is to become familiar with the roles of the individual hormones and the body's natural hormonal cascade (Figure 1).[1]

Figure 1.

Hormonal Cascade
DHEA: dehydroepiandrosterone.
Source: Reference 1.

The adrenal glands and ovaries produce a series of hormones that are derived from LDL cholesterol. After being converted to pregnenolone, the hormone cascade separates into two chains; one chain forms progesterone, aldosterone, and cortisol, and the other forms dehydroepiandrosterone (DHEA), testosterone, and estrogen.[1]


Often thought of as a single female sex hormone, estrogen actually encompasses to a group of female hormones produced by the ovaries. Estrogen travels throughout the body, enabling hundreds of crucial functions, including temperature regulation, muscle maintenance, blood pressure regulation, decreased plaque accumulation, and many others. Estrogen deficiency may be caused by menopause, whereas excess estrogen may be due to impaired estrogen elimination, lack of exercise, or a diet low in grains or fiber.[1]

There are three different types of estrogen: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, the strongest form of estrogen, has often been referred to as the "estrogen of youth" since it is most abundant in females in their teens and 20s. Estrone, the main form of estrogen produced after menopause, is derived from estradiol and functions similarly, only more weakly. Currently, the only known function of estrone is to serve as a reservoir of estrogen. Estriol is the least active form of estrogen, but it has been found beneficial for vaginal symptoms of menopause (including painful intercourse and vaginal dryness and thinning) and urinary incontinence.[1]

High estrogen levels are believed to be associated with an increased risk of developing breast or uterine cancer. This view is supported by several studies, including the Women's Health Initiative (WHI), that compared estrogen-progestin therapy with placebo in more than 16,000 women. High levels of estrone and estradiol are associated with increased activity in breast and uterine tissue, which is thought to increase the risk of breast and uterine cancer.[2] Estriol is much less active in breast and uterine tissues, and it may actually help protect against cancer.[1]


Progesterone is a sex hormone involved in menstruation and pregnancy. Progesterone is produced mostly in the ovaries, with a small amount continuing to be made in the adrenal glands after menopause. Other roles of progesterone include balancing estrogen, building bone, regulating moods, and aiding in proper bladder function. Women with low levels of progesterone may experience anger, irritability, and anxiety.[1]


DHEA and testosterone belong to a group of hormones known as androgens. DHEA, a sex hormone made by the adrenal glands, is one of the first steps in the cascade toward testosterone and estrogen. DHEA serves many purposes, including protecting against cancer, diabetes, obesity, hyperlipidemia, and several other conditions.[1,3] Although testosterone is typically thought of as a male hormone, it is also present in females. Most of the testosterone in the female body is bound to sex hormone-binding globulin, which keeps it from exhibiting an effect on the body. The remaining testosterone helps prevent excess body fat, avoid bone breakdown, improve muscle tone, and increase sexual interest.[1]

Although it is far less common than estrogen deficiency, androgen deficiency is another hormonal imbalance that can occur in females. Androgen deficiency can imply a decrease in any of the major androgens: DHEA sulfate, DHEA, testosterone, and dihydrotestosterone (DHT). DHEA sulfate and DHEA are prohormones, which means that they require activation to testosterone and DHT to exert their effects on sexual function and prevent bone loss. Unlike excess-androgen syndromes such as polycystic ovarian syndrome, there is currently no androgen-deficiency syndrome defined in females, nor are there strict biochemical criteria to diagnose androgen deficiency.[4]