Clinical review: Updates on Menopause

Here is a roundup of the latest research on Menoapuse.

In this article:

Early menopause ups the risk of developing type 2 diabetes

Women who have an early natural menopause have 2.5 times the risk of developing type 2 diabetes as compared to women who have normal menopause reports the results of a large population based study published online July 18, 2017 in Journal Diabetologia.

https://obgynupdated.blogspot.com/2017/07/early-menopause-ups-risk-of-developing.html

Oophorectomy during premenopausal hysterectomy: Evaluating the prevalence

Nearly 1 in 3 women undergo oophorectomy during premenopausal hysterectomy in absence of appropriate indication, reports a study published ahead of print May 8, 2017 in North American Menopausal Society (NAMS) journal Menopause.

https://obgynupdated.blogspot.com/2017/06/oophorectomy-during-premenopausal.html

Loss of estrogen in postmenopausal women puts them at high risk for lumbar disc degeneration.

Declining estrogen levels during perimenopausal and menopausal years is associated with severe lumbar disc degeneration reports a study published online June 12, 2017 in journal Menopause, the journal of The North American Menopause Society (NAMS).

https://obgynupdated.blogspot.com/2017/06/loss-of-estrogen-in-postmenopausal.html

ACP updates guideline for treating Osteoporosis.

According to International Osteoporotic Foundation (IOF), 1 in 3 women over age 50 will experience osteoporotic fractures and nearly 200 million women suffer from osteoporosis worldwide.

https://obgynupdated.blogspot.com/2017/05/acp-updates-guideline-for-treating.html

Polycystic ovarian syndrome increases the risk of subsequent early ovarian aging later in life.

Women with polycystic ovarian syndrome (PCOS) have 8.64-fold increase in risk of developing premature ovarian failure as compared to women who did not have PCOS according to a population based study in forthcoming issue of Journal Menopause. Metformin was found to be effective in reducing such risk.

https://obgynupdated.blogspot.com/2017/05/polycystic-ovarian-syndrome-increases.html

New natural (bioidentical) 17ß-estradiol-progesterone combination available as single soft gel capsules effective in treating postmenopausal symptoms: News from ENDO17

An innovative, investigational combination of 17ß-estradiol and progesterone in a single, oral softgel, was found effective for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. The results of the study were presented at the ENDO 2017, the annual meeting of the Endocrine Society in Orlando, Florida, April 1-4.

https://obgynupdated.blogspot.com/2017/04/new-natural-bioidentical-estrogen.html

New class of drug effective in targeting menopausal symptoms: News from Endocrine Conference 2017.

A new class of drug Neurokinin 3 (NK3) receptor antagonists is highly effective and low risk alternative to hormone replacement therapy(HRT) for treatment of menopausal hot flashes according to a study presented at the ENDO 2017, The endocrine society annual meeting from April 1–4, 2017, in Orlando, FL.

https://obgynupdated.blogspot.com/2017/04/new-class-of-drug-effective-in.html

Menarche ≤11 years and Nulliparity is a risk factor for Premature and Early Menopause.

Women who had their first period at or before the age of 11 are at increased risk for premature and early menopause and the risk is further amplified if the woman is nulliparous according to a large observational study published on January 25, 2017 in Oxford Journal of Human Reproduction.

https://obgynupdated.blogspot.com/2017/03/menarche-11-years-and-nulliparity-is.html

Elective oophorectomy or ovarian conservation at the time of benign hysterectomy?

Hysterectomy is the second most common surgery performed in US after cesarean section.  According to CDC data approximately 600,000 hysterectomies are performed each year. A nationwide study further reported that unilateral or bilateral oophorectomy was performed in 68 percent of women at the time of abdominal hysterectomy, 60 percent at laparoscopic hysterectomy, and 26 percent at vaginal hysterectomy.

Women have an option of undergoing elective oophorectomy (EO) along with benign hysterectomy to reduce the risk of ovarian cancer, thereby reducing a chance of second surgery coupled with decreased perceived   anxiety of breast and ovarian cancer subsequently.But there are negative side effects of this surgical induced menopause such as death, total cancer mortality, osteoporosis, cognitive decline, decreased sexual drive and increased cardiac mishap support conservation of ovarian function.

There is considerable debated going on between EO and ovarian conservation, with strong statements are put forward in favor of each. Currently ACOG recommends “strong consideration should be made for retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer. [However,] given the risk of ovarian cancer in postmenopausal women, ovarian removal at the time of hysterectomy should be considered for these women.”

Arguments in favor of ovarian conservation:

• EO is detrimental for the overall health of women and decreases the life expectancy due to coronary artery disease. In a landmark study by Parker et al using Surveillance, Epidemiology, and End Results (SEER) database, the National center for Health Statistics, the Women’s Health Initiative, and the National Inpatient Sample it was seen that there is no clear cut benefit of EO at any age and women died early due to associate morbidity.
• The neuroprotective benefits of estrogen were seen in multiple studies and was further supported by declining cognitive functions specially in women undergoing EO under 50 yrs.
• EO leads to increase in hip fracture due to decrease in BMD as estrogen levels plummet. This was specifically seen in the light of mass discontinuation of hormone replacement therapy among postmenopausal women when results of Women’s Health Initiation trial published.
• A decrease in sexual desire and function, resulting in quality of life issues and conflict in interpersonal relationship, depression was seen after oophorectomy.

Arguments in favor of EO:

• Ovarian cancer is the fifth leading cause of death among women in US with estimated 22,280 new cases and  14,240 deaths in 2016. A woman’s lifetime risk of ovarian cancer is 1 in 70 or 1.4% with no known effective screening method that could diagnose it at very early stage. Researchers have estimated   that 1000 new cases of ovarian cancer could be avoided if EO is performed in women undergoing hysterectomy in women 40 years and older.
• In women at high risk for ovarian cancer (especially with familial history or genetic predisposition, BRCA1 or BRCA2 mutations) risk-reducing oophorectomy (RRO) reduced cancer specific mortality.
• In general population RRO is an ideal treatment for the prevention of ovarian cancer in women who have known risk factors like being white, never having been pregnant, late age of menopause, and a long estimate number of years of ovulation in absence of effective screening strategies.
• EO leads to avoiding the risk of second surgery after hysterectomy due to adnexal disease or masses.
• Effective replacement therapy available to prevent osteoporosis, cardiac and sexual dysfunctions is being put as a valid argument in support of EO, specifically after the beneficial results of hormone therapy from Women’s Health Initiative studies.
• A recent study by Trabuco et al published in the May issue of Obstetrics and Gynecology has concluded that even if ovaries are spared at the time of hysterectomy, it affects the ovarian reserve as evident by declining levels of Antimüllerian hormone. The study also reported that women undergoing hysterectomy became menopausal 1.9 years earlier than referent patient who has not undergone any surgery.

Despite all these arguments studies have recently documented that of all the hysterectomies performed for benign reason 36%-38% were deemed unnecessary and histologically normal.

So, the decision for EO should be made according to each woman’s individual genetic test results and her risk for developing ovarian malignancy. Age at the time of benign hysterectomy is an important decisive factor. In 2010, recommendations from the Society of Gynecologic Oncologists state “Ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurological disease. Conversely, women at high risk of ovarian cancer should undergo risk-reducing bilateral salpingo-oophorectomy.”

A women’s risk of cardiovascular disease, dementia, osteoporosis, and family history must be taken into account before decisions for EO or ovarian conservation are made in woman considering hysterectomy.

References:

http://www.cdc.gov/reproductivehealth/data_stats/

http://journals.lww.com/greenjournal/Fulltext/2009/11000/Nationwide_Use_of_Laparoscopic_Hysterectomy.13.aspx

http://seer.cancer.gov/statfacts/html/ovary.html

http://www.ncbi.nlm.nih.gov/pubmed/1923173

http://journals.lww.com/greenjournal/Fulltext/2016/05000/Association_of_Ovary_Sparing_Hysterectomy_With.3.aspx

http://www.oncologypractice.com/home/article/high-rates-of-oophorectomy-documented-in-premenopausal-women/36d1b8f86358a40f14c648990ea87471.html?trendmd-shared=0

http://www.obgynnews.com/specialty-focus/gynecology/single-article-page/study-finds-inappropriate-oophorectomy-at-time-of-hysterectomy/afc916acf84845b47cce45ad136610e5.html

A New Paradigm for Prevention of Ovarian Cancer

A New Paradigm for Prevention of Ovarian Cancer

This article is based on a paper by Nezhat R et al in September, 2015  issue of American Journal of Obstetrics and Gynecology.

• It is estimated by American Cancer society that 21,290 new cases of ovarian cancer will be diagnosed in 2015, and 14,180 deaths from ovarian cancer will occur during that period.

• The incidence of ovarian cancer varies geographically. The incidence is high in the Western world. The age-standardized rate (per 100,000 females) is only 3.8 in China, relatively lower than developed countries such the USA (8.8) and Australia (7.7).

• A woman has a 1:70 lifetime risk of being diagnosed with ovarian cancer, the second most common gynecologic malignancy, with the highest mortality rate.

• The majority of ovarian malignancies are epithelial in origin, and within this group the serous type is the most frequent.

• There is currently no effective screening method available for the detection of this disease, which has an overall five-year survival rate of approximately 45%.

• Apart from the genetics and modifiable risk factors responsible for causation of cancer, a new theory by Nezhat et al holds that serous ovarian cancer begins in the Fallopian tube from where it spreads onto the ovarian surface.

• Nezhat and colleagues classify ovarian cancers on the basis of etiology into two groups. Type I cancers originate from various ovarian pathologies (borderline ovarian tumors, endometriomas). These cancers typically have a more favorable prognosis because they are diagnosed at an earlier stage and metastasize more slowly.

• The more frequent type II tumors originate from the fimbriated end of the Fallopian tube and have a less favorable prognosis because they are often diagnosed at an advanced stage.

• Two large collaborative studies have recently called attention to the role of tubal ligation on reducing the ovarian cancer risk.

• The reduction is the greatest for endometrioid and clear-cell carcinoma, and is thought to be associated with the prevention of retrograde menstruation, ovarian seeding by endometrial cells, and inflammation.

• The Society of Gynecologic Oncology also recommends that for women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered in patients at the time of abdominal or pelvic surgery, after completion of child-bearing.

• The interventions called for salpingectomy at the time of hysterectomy, salpingectomy for permanent sterilization instead of tubal ligation, and referral for all patients with high-grade serous cancer for hereditary cancer counseling and genetic testing for BRCA1 and BRCA2 mutations.

• Although still in its infancy, these 3 recommendations are projected to reduce ovarian cancer rates in this province by 40% over the next 20 years.

• These clinical observations and the new recent evidence for the dual pathogenesis of ovarian cancer have set ground for implementing new strategies for screening and prevention programs to reduce the incidence of epithelial ovarian cancer.

• In light of the accumulated data and observations regarding endometriosis and ovarian cancer, Nezhat R. et al propose that it is time to establish criteria for identifying and monitoring women with endometriosis for risk factors and to pursue risk-reducing medical and surgical treatment options in these women.

• At the time of surgical diagnosis and treatment, consideration for complete resection of pelvic endometriosis, salpingectomy, oophorectomy, or hysterectomy should be individualized based on a patient’s age, desire for future fertility, and preoperative consultation with the patient.

• These initiatives, if validated by level 1 evidence, should substantially reduce the risk of ovarian cancer as well as the total mortality risk.

• For now, however, it seems that we may have tools in the future to combat a disease with a high mortality rate.

References:

1. http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf

2. Pasalich M, Su D, Binns CW, Lee AH. Reproductive factors for ovarian cancer in southern Chinese women. Journal of Gynecologic Oncology. 2013;24(2):135-140. doi:10.3802/jgo.2013.24.2.135.

3. Hanna L, Adams M. Prevention of ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2006;20:339-362.

4. Freedman J. Ovarian cancer: current and emerging trends in detection and treatment. New York: Rosen Publishing Group; 2009.

5. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

6. http://www.ajog.org/article/S0002-9378%2815%2900325-7/fulltext

7. http://www.medscape.com/viewarticle/853973#vp_2