HRT to treat symptoms of menopause

Menopause is an event that naturally occurs in all women from around the age of 40 onwards. It is characterised by the lack of periods and concurrent reduction of oestrogen and progesterone levels in the blood, which has a wide range of effects on the body.

How is menopause diagnosed?

Symptoms of menopause can include hot flushes, night sweats, joint aches and headaches, all of which can be particularly bothersome in day-to-day life. Menopause is typically diagnosed retrospectively based on the presence of these symptoms, the patient’s age and frequency of periods. However, the US Food and Drug Administration (FDA) has recently permitted the marketing of the first diagnostic kit that can identify patients who are entering their menopausal transition. The technology uses declining levels of anti-Müllerian hormone concentrations in the blood as a marker, thus allowing treatments to be administered promptly.[1]

What is the current treatment landscape for menopause?

Lifestyle changes such as healthy eating, reducing alcohol intake and regular exercise can sometimes help to alleviate menopausal symptoms. In some cases, hormone replacement therapy (HRT) may be prescribed to top-up oestrogen and/or progesterone levels, aiming to restore the hormonal balance. HRT for menopause is a key area of interest and has been the focus of recent major randomised controlled trials (RCTs).[2]

What do the experts say on HRT?

In theory (and in practice), HRT has the potential to reverse the symptoms of menopause. However, there have been some concerns on the side effects associated with this type of treatment. Although both the North American Menopause Society (NAMS)[3] and European Menopause and Andropause Society (EMAS)[4]  consider HRT to be the most effective treatment for vasomotor symptoms, genitourinary syndrome of menopause and preventing bone loss and fracture, they do highlight the risk of cardiovascular events, endometrial hyperplasia and certain cancers associated with HRT. To tip the benefit-risk balance in our favour, the appropriate dose, formulation and route of administration should be all individualised to the patient at treatment initiation and adapted throughout treatment where necessary. [2]

How is the field of HRT evolving?

Following the publication of initial findings from an RCT by the Women’s Health Institute (WHI) there were fears that HRT increases the risk of breast cancer and cardiovascular disease. As a result, the use of non-FDA-approved compounded hormone therapy in the US increased and FDA-approved hormone therapies declined.[5] However, subsequent detailed analyses showed that these fears were misrepresented and the risks were only applicable to a small subset of patients. Since then, it has been an upward battle to turn the field around and encourage HCPs and women to consider the evidence and opt for approved therapies, rather than taking non-approved compounded therapies with unknown risks.

The change is upon us, slowly but surely

The US has recently seen the approval of the first bioidentical combination HRT containing 17β-estradiol and progesterone (chemically-identical to those found in the body) for the treatment of moderate to severe vasomotor symptoms associated with menopause in women with a uterus. The REPLENISH trial demonstrated that the frequency and severity of vasomotor symptoms were significantly decreased with the combo therapy compared with placebo and no endometrial hyperplasia events were reported over the 12-month trial period.[6] This approval marks a milestone in the field of HRT and could be the turnaround needed to ensure women receive the most appropriate treatment for their menopause.

Based on the recent diagnostic testing and HRT approvals, could it be time to revisit the guidelines? What are the learnings from REPLENISH and other pivotal trials that can be applied to pipeline therapies? What else do we need to do to pull ourselves out of the shadows of the WHI trial? We will be at the COGI Congress to find out more! The congress will be held in London on 23rd-25th November and we will be sharing with you the latest expert opinions and discussions in a special session on “HRT: Where we came from. Where are we going?”. We will also be posting a number of other blogs before, during and after the Congress that will build on the latest clinical and real-world developments in Women’s Health. So stay tuned for more!

 


Sources:

[1] US FDA. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624284.htm [Accessed October 2018].

[2] Woods NF and Utian W. Quality of life, menopause, and hormone therapy: an update and recommendations for future research. Menopause. 2018 Jul;25(7):713-720.

[3] The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753.

[4] Armeni E, Lambrinoudaki I, Ceausu I et al. Maintaining postreproductive health: A care pathway from the European Menopause and Andropause Society (EMAS). Maturitas. 2016 Jul;89:63-72.

[5] American College of Obstetricians and Gynecologists. Compounded bioidentical menopausal hormone therapy. Committee Opinion No. 532. Obstet Gynecol 2012;120:411–5.

[6] Lobo RA, Archer DF, Kagan R et al. A 17b-Estradiol–Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women. Obstet Gynecol. 2018 Jul;132(1):161-170.