Artículo de Revisión
Traducción y comentarios: Dra. Claudia Rey1
Summary
Recently, Tang et al. [1] carried out a randomized, open-label, multicenter clinical trial aimed at comparing the efficacy and safety of oral estradiol (OE2) and transdermal estradiol (TE2) for the treatment of menopausal symptoms by evaluating changes in scores of the Kupperman Menopausal Index (KMI) and the Menopause Rating Scale (MRS). The trial was conducted in 10 medical centers in China with a follow-up period of 24 weeks, including 257 healthy perimenopausal or postmenopausal women aged 40 to 55 years, with intact uterus and with moderate or severe menopausal symptoms, as defined by a score of ≥ 14 in the modified KMI (KMI validated for China). The MRS was also used to assess symptoms [2] together with the KMI at baseline and at each visit (4, 12 and 24 weeks) after the initiation of treatment. Participants were randomly assigned to one of two groups: one received TE2 (2.5 g/day (n=128), and the other OE2 (n=129, oral estradiol valerate 2 mg/day); both combined with micronized progesterone (200 mg/day) for 24 weeks. The results showed significant improvements in KMI and MRS scores in both groups (p<0.001). There were no significant differences in KMI scores between groups at any time point, but MRS scores showed statistical differences in favor of TE2 at 12 and 24 weeks (p=0.005 and p=0.011, respectively). The incidence of adverse effects was similar in both groups. The authors conclude that both TE2 and OE2 are effective and safe in relieving menopausal symptoms. Although the differences in efficacy were minimal, treatment should be tailored to the needs of each woman.
Commentary
Comparing the advantages and disadvantages of Menopausal Hormone Therapy (MHT) according to the route of administration has been a research topic of great interest in recent years. Currently there are no relevant well-designed and high-quality studies carried out in Chinese women. Therefore, the authors designed the present clinical trial [1] to investigate the impact of the administration route of E2 on efficacy and safety in early menopausal women. Both administration routes were shown to be highly effective in relieving menopausal symptoms, as assessed by the modified KMI and the MRS. Although no significant differences in KMI were observed between groups, MRS scores at 12 and 24 weeks indicated a slight advantage for TE2. These results underline the importance of considering the appropriate measurement tool when assessing therapeutic response and suggest subtle differences in the clinical effects of both formulations.
Regarding safety, the incidence of adverse events was similar in both groups, with breast tenderness being the most common side effect. Previous studies have shown that breast tenderness is a common but bothersome adverse effect of MHT, with an incidence of approximately 10% [3,4]. There was one case of breast cancer in the transdermal group, highlighting the need for appropriate monitoring when prescribing MHT to women, especially those with pre-existing risk factors. TE2 showed metabolic advantages, such as less impact on hepatic metabolism due to the absence of the first-pass effect, making it particularly appropriate for women at high risk of venous thromboembolism, hyperlipidemia, or metabolic syndrome [5].
This study reinforces the use of MHT as an effective and safe option to relieve menopausal symptoms, recommending that women with bothersome symptoms accept receiving MHT for their relief, and given the fact that currently the rate of MHT use in China remains low and is often used only on a short-term basis [3,4]. This study is a significant contribution to the management of menopausal symptoms in Asian women. It also highlights the importance of personalizing treatment according to the individual needs of women. The advantages of TE2, in terms of hormonal stability and lower metabolic impact, make it a recommended option in women with specific risks, while OE2 remains a viable alternative for other ones.
Despite its strengths, such as the randomized design and the use of validated assessment tools, the study has limitations, such as a relatively small sample size, short duration of follow-up, and exclusion of other ethnic groups. Long-term studies are needed to assess less frequent risks, such as breast cancer or cardiovascular events, associated with MHT use.
In conclusion, this study reinforces the efficacy and safety of OE2 and TE2 for the management of menopausal symptoms. Selecting the route of administration should be based on an individualized approach, considering both women’s clinical profile and her personal preferences. Future research with more diverse populations and prolonged follow-ups will be essential to expand the applicability of these results and optimize clinical recommendations for the use of MHT.
Take home key points
- Both estradiol formulations (oral and transdermal) were effective and safe in relieving menopausal symptoms, with minimal differences in efficacy, allowing a personalized choice according to the individual needs of each woman.
- The transdermal route could offer additional advantages in women with metabolic or hepatic risk, standing out as a preferred option in certain clinical cases.
Claudia Rey, MD, FACOG
Past President of AAPEC (Argentinian Association for the Study of the Climacteric)
Director of the Argentine School of Climacteric of AAPEC
References
- Tang R, Xie Z, Ruan X, Zhang Z, Ren M, Wu J, Shu K, Shi H, Xie M, Lv S, Yang X, Chen R, Yu Q. Changes in menopausal symptoms comparing oral estradiol versus transdermal estradiol. 2024;27(2):171-177.
https://pubmed.ncbi.nlm.nih.gov/37942806/
- Heinemann K, Ruebig A, Potthoff P, Schneider HP, Strelow F, Heinemann LA, Do MT. The Menopause Rating Scale (MRS) scale: a methodological review. Health Qual Life Outcomes. 2004;2:45.
https://pubmed.ncbi.nlm.nih.gov/15345062/
- Crandall CJ, Karlamangla A, Huang MH, Ursin G, Guan M, Greendale GA. Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy. Arch Intern Med. 2006;166(15):1578-1584.
https://pubmed.ncbi.nlm.nih.gov/16908790/
- The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. 2017;24(7):728-753.
https://pubmed.ncbi.nlm.nih.gov/28650869/
- Goodman MP. Are all estrogens created equal? A review of oral vs. transdermal therapy. J Womens Health (Larchmt). 2012;21(2):161-9.
https://pubmed.ncbi.nlm.nih.gov/22011208/
1. Médica Ginecóloga. Ex Presidente de AAPEC (2019 - 2020)
Especialista Consultor en Climaterio
Co - Directora Escuela Argentina de Climaterio de AAPEC
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