Menopausal hormone treatment MHT is the best method for reducing menopausal symptoms. The duration, myths, benefits and risks associated with the menopausal hormonal therapy are penned down in this article. 

Menopausal Hormone Therapy

Menopause is the permanent cessation of menstrual periods for 12 months. The most common symptom is hot flashes experienced by up to 80 per cent of women. Mood symptoms may also occur in the menopausal transition. Many women also have vaginal dryness, dyspareunia, and sexual dysfunction (genitourinary syndrome of menopause GSM) in the late menopausal transition and postmenopausal years.

Patient selection 

In healthy, peri/postmenopausal women with moderate to severe vasomotor symptoms impacting sleep, quality of life, or ability to function, and who are within 10 years of menopause (or <60 years of age), MHT can be prescribed [1]. For the management of GSM low-dose vaginal estrogen should be given. MHT should be avoided in women with a history of breast cancer, coronary heart disease (CHD), a previous venous thromboembolic (VTE) event or stroke, active liver disease, or those at high risk for these complications [2]. MHT is not used for the prevention of chronic disease (osteoporosis, CHD, or dementia).

Duration of MHT

Standard recommendations for MHT use are three to five years. In cases of primary ovarian insufficiency (POI), MHT should be given for a longer duration till the average age of menopause. Nonhormonal options should be given if hot flashes recur after stopping estrogen. If not relieved, then MHT can be restarted at the lowest dose possible.

Myths about MHT

Women's Health Initiative (WHI): The Women's Health Initiative (WHI) is a landmark research study focused on two hormone therapy (HT) trials (unopposed estrogen and continuous, combined estrogen-progestin therapy versus placebo) in approximately 27,000 postmenopausal women (mean age 63 years). According to this study, several adverse outcomes, like an excess risk of CHD, stroke, venous thromboembolism (VTE), and breast cancer, were associated with the MHT. [3, 4, 5].

United States Preventive Services Task Force (USPSTF): The USPSTF meta-analysis was also against the use of MHT for the prevention of chronic conditions [6, 7, 8]. Similar results were noted in a meta-analysis of 22 studies [8]. Both included the WHI, and the mean age of subjects was >60 years.

Many myths and misunderstandings have surrounded Menopausal Hormone Therapy (MHT) after the WHI research data were published. But WHI demonstrated the adverse effects of MHT in older postmenopausal women (over age 60 years). Later, detailed analyses proved MHT to be beneficial for women who seek medical therapy for menopausal symptoms and are in their late 40s or 50s.

1. Myth: MHT causes significant weight gain. Women using MHT do not gain more weight than those who do not [9].
2. Myth: MHT raises the risk of coronary heart disease. The overall rate of coronary events was increased with combined MHT (conjugated equine estrogen-medroxyprogesterone acetate) [4,10,11]. Detailed analyses of WHI showed women who were <10 years since menopause or between the ages of 50 and 59 years did not have an excess risk [10] or possibly had a risk reduction [12].
3. Myth: MHT raises the risk of Stroke: In the WHI, combined MHT showed a 31 per cent increase in stroke risk compared to placebo, while stroke risk was significantly increased with conjugated equine estrogen versus placebo [4]. However, the extremely low absolute excess risk of stroke was seen in women ages 50 to 59 years (0.15 versus 0.13 cases per 100 women per year for HT and placebo, respectively) [10].
4. Myth: MHT raises the risk of Venous thromboembolism. The rate of VTE in the WHI increased with MHT when compared with placebo [4,13]. It was also seen in the Heart and Estrogen/Progestin Replacement Study (HERS) trials. But for women aged 50 to 59 years, the ideal candidates of MHT the risk is low. The estimates of excess VTE risk in one analysis were 4.7 and 1.3 additional cases per 1000 women per five years of combined estrogen-progestin or unopposed estrogen use, respectively [14].
5. Myth: MHT may cause mortality: An 18-year follow-up report from the WHI hormone therapy (HT) trials showed that [15] all-cause mortality was similar in women taking MHT or placebo. MHT reduced all-cause mortality in women ages 50 to 59 years during the intervention phase and possibly after 18 years of follow-up.
6. Myth: MHT dramatically increases breast cancer risk: In the Women's Health Initiative (WHI), the risk of invasive breast cancer was significantly increased with combined hormone therapy (HT) at an average follow-up of 5.6 years [16]. But the baseline risk of breast cancer is lower in women aged 50-59 or those who start treatment within 10 years of menopause [17].
7. Myth: MHT increases the risk of Ovarian cancer. A nonsignificant increase in the risk of ovarian cancer was observed in the WHI with combined estrogen-progestin therapy [18]. But the absolute risk of ovarian cancer with MHT is very low, so it should not be a major consideration for MHT for symptomatic relief.
8. Myth: MHT increases the chances of Endometrial hyperplasia and carcinoma. The absolute risk of endometrial carcinoma in women taking unopposed estrogen increases to approximately 1 in 100 compared to 1 in 1000 postmenopausal women not on MHT. But this can be prevented by concurrent therapy with a progestin. [18,19,20]. In the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, combined estrogen-progestin therapy led to marked reductions in the incidence of endometrial lesions when compared with unopposed estrogen [20].

Benefits

1. Reduced risk of osteoporotic fractures: The risk of osteoporotic fracture with MHT versus placebo was reduced at the hip and at the vertebrae, and wrist [4,21].
2. Reduced risk of type 2 diabetes mellitus: For women ages 50 to 59 years on MHT, the estimate of benefit in one analysis was 11 fewer cases per 1000 per five years of use. [14].
3. Reduced risk of Colorectal cancer: In the WHI, the risk of colorectal cancer was reduced with combined MHT use, that is 43 versus 72 cases in the hormone and placebo groups, respectively; [22].
4. Reduced risk of recurrent urinary tract infections: vaginal estrogen may also be beneficial for reducing the frequency of recurrent urinary tract infections in postmenopausal women [23]. It can be given to postmenopausal women not taking oral estrogen who have three or more recurrent urinary tract infections per year [24].
5. Reduced risk of osteoarthritis: In a cross-sectional study of over 4000 women, those receiving long-term estrogen therapy (≥10 years) had a 40 per cent lower risk of hip osteoarthritis than those who had not received estrogen. Similar results were found in a prospective analysis of the Framingham cohort [25] and the WHI trial [26].

Other Risks

1. Gallbladder disease: The WHI and the HERS trial found a significantly increased risk of biliary tract disease among women using oral estrogen therapy [27]. The authors calculated that for every 185 women receiving hormone therapy (HT), one additional woman had biliary tract surgery per year [28].
2. Lung cancer: Women on combined estrogen-progestin therapy who developed non-small cell lung cancer (NSCLC) had a significantly shorter survival compared with those given a placebo.
3. Urinary incontinence: The HERS and WHI trials have reported that oral hormone therapy (HT) worsens incontinence.
4. Bronchospasm: Estrogen therapy may be associated with the onset of asthma [29].
5. Systemic lupus erythematosus: Postmenopausal estrogen use may increase the risk of flare in women with established SLE, but these flares tend to be mild to moderate, not severe [30,31]. Estrogen therapy should be avoided in patients who also have antiphospholipid antibodies because of the increased risk of thromboembolic events.
6. Uterine leiomyomas: A systematic review including five randomised controlled trials found that MHT caused myoma growth, but this typically occurred without clinical symptoms [32,33]. Thus, the presence of leiomyomas is not a contraindication to MHT nor associated with new symptomatic fibroids in most women.
7. Epilepsy: In a report of 42 menopausal women with epilepsy, MHT was associated with an increase in seizure frequency [34]. Although these data are not sufficient to recommend that women with seizures not be offered HT, women with seizures who are treated should be monitored carefully.

Fig.1 Risks and benefits of menopausal hormone therapy (MHT)

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

The author of this article: Dr Supriya Chaubey is an Assistant Professor at HIMSR, New Delhi.