The new position statement from the North American Menopause Society provides updates and clarification on hormone replacement research since their last statement in 2012. The 2017 statement takes into account new evidence from recently conducted clinical trials as well as the Women’s Health Initiative (WHI) and other previous studies. NAMS gathered an advisory panel that included clinicians and researchers who are experts in women’s health and menopause to evaluate the current evidence on hormone replacement. They concluded that “hormone therapy is the most effective treatment for VMS [vasomotor symptoms] and GSM [genitourinary symptoms] and has been shown to prevent bone loss and fracture.”
Women’s Health Initiative
The initial results of the WHI, which were widely reported by the media, made many women hesitant about trying hormone replacement. With significant analysis and further research since then, the evidence shows that hormone replacement is effective and that the benefits outweigh the risks for most women.
While the WHI continues to be used as it is the only large-scale trial of its kind, many other trials were considered in the NAMS position statement. The WHI is limited in that it only used oral administration and not topical and only one formulation of conjugated equine estrogen and progestogen (synthetic progesterone). Additionally, the group included a limited number of women who were in the ideal range for receiving hormone replacement – which is younger than 60 years and within 10 years of the onset of menopause.
Good Benefit-Risk Ratio with Hormone Therapy
The evidence is clear that hormone replacement helps with vasomotor symptoms of menopause (hot flashes, night sweats) and genitourinary symptoms, and prevents bone loss and fracture. According to the NAMS statement, the benefit-risk ratio is optimal for patients under 60 years of age who have had menopause start within 10 years. For these patients, therapy with estrogen is recommended. If hormone replacement is started 10 years or later after the onset of menopause, the risk of cancer and other adverse effects increases. The NAMS statement concludes:
“Absolute attributable risks for women in the 50- to 59-year-old age group or within 10 years of menopause onset are low, whereas the risks of initiation of HT for women aged 60 years and older or who are further than 10 years from menopause onset appear greater, particularly for those aged 70 years and older or who are more than 20 years from menopause onset, with more research needed on potential risks of longer durations of use.”
Additionally, the statement clarifies the risk of breast cancer from hormone replacement therapy for women who were in the WHI study. The risk is compared to the risk of drinking one glass of wine daily:
“The attributable risk of breast cancer in women (mean age, 63 y) randomized to CEE + MPA in the WHI is less than 1 additional case of breast cancer diagnosed per 1,000 users annually, a risk slightly greater than that observed with one daily glass of wine, less than with two daily glasses, and similar to the risk reported with obesity, low physical activity, and other medications.”
Estradiol vs. Conjugated Equine Estrogen
While the position statement made no conclusions about whether estradiol or conjugated equine estrogen (CEE) was more effective at treating vasomotor symptoms, it did note that estradiol produces different cognitive outcomes. Estradiol has been shown to provide greater antidepressant and anxiety-reducing effects than CEE. Estradiol is what is sometimes referred to as a “biodientical hormone,” since it is closer to hormones produced naturally in a woman’s body. It is most often synthesized from wild yams, while CEE is made from the urine of pregnant mares.
Progesterone and Unopposed Estrogen
If systemic estrogen is administered it can increase the risk of endometrial cancer if it is not opposed by progesterone. In most cases, unless a woman has had a hysterectomy, systemic estrogen is prescribed in combination with progesterone. Sometimes a selective estrogen-receptor modulator (SERM) like bazedoxifene is used with systemic estrogen therapy instead of progesterone.
When progesterone is used with estrogen therapy, the risk of endometrial cancer is no greater than in women who do not receive therapy. While the WHI used synthetic progestogens, it has been suggested in observational studies that micronized progesterone (“bioidentical” progesterone) may result in less risk of breast cancer compared to synthetics.
Low-Dose Vaginal Estrogen Therapy
The NAMS position statement notes that if genitourinary symptoms are not relieved with other forms of treatment, a low-dose vaginal estrogen cream is recommended. This kind of cream results in lower systemic absorption than an orally administered capsule, and does not require progesterone be taken to prevent endometriosis. Vaginal dryness and atrophy can often be resolved with the use of a topically applied, low-dose estrogen cream.
Compounding and Hormones
The NAMS position statement does not recommend the use of compound hormones except in cases where the formulation the patient needs is not available commercially. It mentions specifically cases where a woman has allergies to certain ingredients or needs a dosage that is not found in any FDA-approved product as cases where a compounding pharmacy should be used.
However, while the statement focuses mostly on estrogen therapy, it does not discuss other hormones that many healthcare professionals prescribe for their patients. A compounding pharmacy is able to combine estradiol, estriol, progesterone, testosterone, and DHEA together into one cream. Commercially available treatments only include estradiol and progestogens.
Although NAMS recommends the use of FDA-approved hormones, they do state that “with interim guidance on compounding safety and quality control from FDA, quality control of compounded HT may improve.” Park Compounding Pharmacy in particular adheres to USP-800, a new quality standard for compounding products that require a more controlled environment. A USP-800-compliant room in our pharmacy was built specifically for compounding hormones.
Continuing Research on Hormone Therapy
The perception of hormone replacement has recovered significantly from the bad publicity following the initial results of the WHI. Healthcare providers and women entering menopause are much more likely now to consider it as an option. While research continues to be done that will improve how hormones are prescribed, it is clear from the NAMS position statement that hormone therapy is the most effective treatment available for alleviating the symptoms of menopause.