Showing posts with label estrogen and bazedoxifene (CE/BZA). Show all posts
Showing posts with label estrogen and bazedoxifene (CE/BZA). Show all posts

Friday, July 7, 2017

NAMS updates its position statement on HRT, clearing five critical areas of confusion.

courtesy: www.renewedvitalitymd.com
The North American Menopause Society has updated its position statement regarding menopausal and post-menopausal hormone therapy, replacing the earlier statement issued in 2012.

Instead of prescribing, “lowest dose for the shortest period of time” which may be harmful for some women, the new emphasis is on “appropriate dose, duration, regimen, and route of administration that provides the most benefit with the minimal amount of risk.”

The new position statement was published online June 21 in NAMS’s Journal Menopause.

Hormone Replacement Therapy remains the most effective treatment for vasomotor symptoms (VMS) and Genitourinary symptoms of menopause (GSM) and helps prevent osteoporosis and fractures.

The US FDA approved indications for starting HRT are bothersome vasomotor symptoms and genitourinary symptoms, Estrogen deficient states caused by premature ovarian insufficiency (POI), hypogonadism and castration and prevention of bone loss.

Women who are seeking relief for bothersome vasomotor symptoms are offered conjugated equine estrogen (CEE) if they already had hysterectomy or it is paired with a progestogen or with bazedoxifene, a selective estrogen-receptor modulator (SERM), to protect users against endometrial cancer.


The statement authors also suggest that micronized progesterone at a dose of 300 mg at bedtime can be an effective treatment to reduce hot flashes and night sweats and improves sleep.

Low dose, intravaginal estrogen preparation is the treatment of choice for women with vulvovaginal atrophy (VVA), because of minimum systemic absorption. For women who are intolerant to estrogen, ospemifene or intravaginal DHEA is equally effective in relieving the symptoms of atrophy. This preparation also bring relief from urinary symptoms.

Systemic Hormonal therapy is not effective in improving urinary incontinence and on the other hand may exacerbate stress incontinence.

HRT in women who have undergone surgical menopause or POI should be started early and at least continued till the age of 52 years.

An important update in this statement was about starting HRT in women with BRCA 1/2 mutation. Dr. JoAnn V. Pinkerton, NAMS executive director said, "For BRCA-positive women without breast cancer who have undergone risk-reducing bilateral salpingoophorectomy, observational data suggest that systemic HRT to the median age of menopause may decrease health risks associated with premature loss of estrogen without increasing breast-cancer risk. "

Physician should be cautious in starting HRT in women who are 10 years past menopause or 60 years old at the time of initiating HRT. In these group of women, the benefit/risk ration is less favorable than for younger women because of increased risk of stroke, CVD, venous thromboembolism and dementia.

If the women are already on HRT, the therapy need not be discontinued abruptly at age 60 or 65 years. It may be continued past 65 years of age for persistent hot flashes, prevention of osteoporosis, and quality-of-life issues, with an open dialogue with the patients about the risk and benefits of HRT at this age.

Once HRT is stopped, in 50% of women, vasomotor symptoms will recur, irrespective of age of starting the therapy or duration of therapy quoted the authors of the statement.

And, nearly all women, will lose [bone-mineral density], with increased risk of bone fractures and excess mortality from hip fracture," they also point out.

Dr Pinkerton added "And the risks of longer use of HRT may be minimized with the use of lower doses of both estrogen and progestogens, the use of transdermal therapies to avoid hepatic first-pass effect, or the combination of conjugated estrogen paired with the SERM bazedoxifene, which provides endometrial protection without the need for a progestogen."

NAMS has also released a patient information sheet called ‘MenoNote’ that simplify the facts and help women to decide using HRT. The ‘MenoNote’ is available on NAMS website. It can be accessed here.




Friday, September 23, 2016

New International Menopause Society (IMS) guidelines affirms the safety of menopausal HT.

The International Menopause Society (IMS) recently released 2016 Global Consensus Statement on Menopausal Hormone Therapy (MHT).[1]  The IMS brought together 7 international societies, including European Menopause and Andropause Society and the North American Menopause Society to formulate comprehensive, evidence based guidelines with practice essentials to help and guide physicians across the globe in managing women through menopause transition and beyond.

The guidelines are aimed at helping women across the globe to prevent chronic diseases due to aging along with treatment of troublesome menopausal symptoms. 

The term Menopausal Hormone Therapy (MHT) includes estrogen, progesterone and combined therapies.

The recommendations simply provide an overview of basic principles of hormone therapy which can be modified and adapted according to the geographical region, country specific belief and practices, basic infrastructure of healthcare and the variation and availability of the hormones. It also simply provides consensus and is not a replacement for the detailed guidelines issued by each individual societies.

Professor Rod Baber, IMS President, commented “I believe the new Global Consensus is a major step forward in the management of menopausal women as it provides women and their doctors with internationally endorsed guidance”.[2]

General principles that governs the use of MHT


The option of starting MHT should be decided according to the need of each patient depending upon age, time elapsed since menopause, the symptoms, risk of VTE, breast and gynecological malignancies and CVD.

It should be a part of overall life style change and management including diet, exercise and smoking cessation for prevention of postmenopausal osteoporosis.

MHT include a range of hormonal products that can be administered by various routes. It includes Tibolone or CE/BZA too when available. Each product has its own side effects, and risk/benefit rations.

MHT should always begin with the lowest possible dose that alleviates the symptoms with minimum side effects. The route of administration should be tailored to individual need, preference and side effects. 

The benefit/risk ratio should be assessed annually for each patient. The duration of the treatment should be planned accordingly with the lowest possible dose schedule. Some women may require longer duration of treatment for relief of Vaso Motor symptoms (VMS).

Use of estrogen as single systemic agent is only advocated in case of patients who have undergone hysterectomy, concomitant use of progesterone is always advocated with intact uterus unless CE is combined with BZA for uterine protection. 

Testosterone only therapy or in combination with MHT is only indicated in selective postmenopausal women with sexual interest/arousal disorder.

Use of custom compound hormone therapy is not recommended because of batch to batch variability, lack of regulation standards for safety, efficacy and purity.  

Safety data on use of MHT for breast cancer survivor is limited currently. It’s use in such patients can only be undertaken after discussing it with patient’s oncologist when complementary options have exhausted.   

Benefit/risk profile for MHT


Quality of life, sexual satisfaction, mood changes, joint pain and sleep disturbances may improve with MHT.

MHT with Tibolone and combination of Conjugated Equine estrogen and bazedoxifene (CE/BZA) is effective in treatment of osteoporosis. It has consistently seen to be effective in reducing the risk of vertebral, hip and other osteoporosis-related fractures in post-menopausal women.

MHT is the only therapy that is effective in preventing fractures in postmenopausal women with mean T-score in normal or osteopenic range. It should be initiated before the age of 60 or 10 years within menopause for at risk women for osteoporosis. 

If started after the age of 60 years, it is considered the second line of therapy and risk/ benefit ratio should be compared with other first line drugs.

The most effective treatment of VMS at any age is Tibolone and combination of Conjugated Equine estrogen and bazedoxifene (CE/BZA). Symptomatic women derive maximum benefits if treatment is started within 10 years of menopause or before the age of 60 years.

Vulvovaginal atrophy(VVA) is now considered a component of genitourinary syndrome of menopause (GSM). MHT including Tibolone relieves the symptoms of VVA. Topical estrogen preparations are first line of treatment in patients with only local vaginal dryness, dyspareunia or recurrent UTI. Ospemifene, a selective estrogen receptor modulator (SERM) is also licensed in some countries for treatment of dyspareunia due to VVA.

Many observational studies, RCTs and meta-analysis provides data that shows consistent benefits in standard dose estrogen alone group as compared to estrogen plus progestogen MHT in decreasing myocardial infarction and all-cause mortality when initiated before age of 60 or within 10 years of menopause.

The risk of VTE and ischemic stroke increases with oral MHT as compared with transdermal therapy (0.05 mg twice weekly or lower) when started before the age of 60 years.

The risk of breast cancer with MHT in women over the age of 50 years is a complex issue. Estrogen only MHT in women with hysterectomy shows a lower risk as compared to combine therapy the medroxyprogesterone acetate in the women’s health initiative study (WHI). However, the risk of < 1.0 per 1000 women per year is less than that associated with sedentary life style, alcohol consumption and obesity.

Women who experience a natural or iatrogenic menopause before the age of 45, particularly before the age of 40 face a consistent high risk for cardiovascular disease, osteoporosis, mood disorders and dementia. Results of observational studies have shown that these women benefit from MHT, but they have to be confirmed by RCTs. MHT can be prescribed till the age of natural menopause. 

In women with major depressive disorders, antidepressant therapy remains the first line of treatment, although MHT can be used to improve mood in women with anxiety/depressive symptoms.  MHT initiated in early menopause and after the age of 65 years also does not have significant effect on cognition and increase the risk of dementia.  Although some observational studies have shown that early initiation may prevent Alzheimer’s disease in later life.




[1] http://www.imsociety.org/manage/images/pdf/fd28270c02bdca95a58a471e1719e9b4.pdf
[2] http://www.imsociety.org/manage/images/pdf/d9cfd8c2b902d63b0c1bb0ada805240d.pdf