Twelve important risk factors for Uterine Fibroid identified: A systematic review

First and only systematic review conducted so far to know the prevalence and risk factors for developing Uterine Fibroid (UF), identified race and ovarian hormone exposure as the most important determinants of fibroid development. The review was published recently in BJOG.

Uterine fibroids are most common benign neoplasm in women and nearly affect 2/3 of women before menopause, but largely remain undetected as only 25% cause symptoms that warrant treatment.

They are also the number one cause of gynecological hospital admissions and also an important indication for hysterectomy.

A literature search identified 60 studies that were eligible to be included in the review. There was considerable variations in type of studies, some reported single center experience while mostly were registry based studies. Studies included cohort and case control studies with international or local population with women from different race and ethnicity.

Fibroids were diagnosed by pelvic examination, Ultrasound or at the time of surgery.

There was a wide range in incidence of UF, and varied between 217–3745 cases per 100 000 women-years while the prevalence was between 4.5% to 68.6%.

After analysis of data, broadly 30 factors were identified that increased a woman’s risk of developing UF, of which  12 were of considerable magnitude.

Risk Factors:

Demographically, black race is important risk  factor and increases the risk by 2-3-fold as compared to  whites, followed  by age. 

Age increases the risk by nearly 10 folds,  for women between age the  40 -60 years as compared to women in their 20s. 

A positive family history also predisposes the women to higher risk for UF.

More than 5 years since child birth puts you at higher risk as compared to woman who has recently given birth.

Premenopausal women have 3-5 times increased risk as compared to postmenopausal women.

Women who are diagnosed with hypertension are 5 times the risk as compared to their normotensive counterparts.

Consuming food with additives and Soyabean increases the risk by 2.5times.

Protective Factors:

Increased parity (more than 3 children) is protective against UF and lowers the risk by 80% as compared to Nulliparous woman.

Smoking was found to be protective, but only in women with low BMI

Oral and injectable contraceptives protect against UF and reduces the risk by nearly 20-50%.

This study supports the view that genetic and ovarian hormones are two important risk factors for development of UF. The genetic aspect cannot be modified, but life style and hormonal modification can reduce the risk of fibroid development.

In an accompanying commentary, Vercellini P and Frattaruolo MP stress the importance of therapies using selective progesterone receptor modulators (SPRMs) as an alternative to invasive treatments for fibroid associated menorrhagia and volume symptoms.

This study has identified important risk factors that can be used by physicians in clinical settings and researchers for further drug and treatment development.

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Commentary 

Oral contraceptives use around and during pregnancy does not appear to be teratogenic.

Image in the public domain, courtesy of Wikimedia Commons

2010 saw the 50^th anniversary of the contraceptive pill.

‘The pill’ as it is commonly known was a key player in building women’s current economic role in society as it gave women an unprecedented control over their own fertility.

Oral contraceptives remain the most common method of contraception in most part of the world. According to a CDC Faststats:

• Leading contraceptive method among women aged 15-29: Pill
• Percent of women aged 15-44 currently using the pill: 17.1%

Although the failure rate is 0.1 percent when pills are taken perfectly (same time every day, no missed pills), the actual failure rate is 9 percent over the first year, due primarily to the missed pills, drug interactions, forgetting to restart the pill after the seven-day pill-free interval or illness and results in what is known as breakthrough pregnancy.

photo courtesy: http://www.catholicmatch.com

Studies conducted in the past with high dose preparations have linked various birth defects with first trimester exposure to oral contraceptives. These birth defects involved the vertebrae, anus, heart, trachea, esophagus, kidney and limbs (VACTERL syndrome) (Nora et al, 1976).

After thorough investigation in the later years, these associations have not been substantiated. These studies were mainly focused on use of the OC during the first trimester.  No studies were found that studied the effect of exogenous hormones immediately before and around the time of conception or immediately after conception.

This prospective observational cohort study conducted by Brittany M Charlton from the Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts and her colleagues from Denmark was published on line on January 6, 2016 in British Medical Journal and aims to study the association between use of oral contraceptives around pregnancy time and resulting congenital malformations in the fetus.

They used Medical Birth Register records from 1997 to 2011 (880,694 live births) and Danish National Prescription Register and collected prescription data on the use of oral contraceptives. The investigators assumed that women who filled their prescriptions were exposed to oral contraceptives.

The women were divided into 4 groups, No oral contraceptive exposure, >3 months before pregnancy onset (reference group), 0-3 months before pregnancy onset (that is, recent use), and after conception. The two primary exposures of interest were after conception and recent use before pregnancy onset.

Any major birth defect was the primary outcome and subgroups of major birth defects categorized by organ system were the secondary outcomes.

Previous studies have observed associations between oral contraceptive exposure and 4 subgroups of congenital anomalies of hypoplastic left heart syndrome, gastroschisis, limb defects, and urinary tract anomalies.

Logistic regression was used to o estimate prevalence odds ratios of any major birth defect as well as categories of birth defect subgroups.

It was seen that the prevalence of major birth defect was consistent at 25 per 1000 live births across all the four groups. The study did not find any increase in the 4 birth defects that earlier studies have shown a link with.

The study lacked the statistical power for different formulations of oral contraceptives and specific subgroup of birth defects, but was very strong when it comes to examining the association between birth defects and the timing of oral contraceptives use.

It also stands at par with other studies conducted earlier, documenting no increase in birth defects after the use of oral contraceptives.

It also assures the patients and healthcare providers about no association between the oral contraceptive use and increased risks of malformation, as estimated 9% of oral contraceptive users become pregnant in the first year of use; many more women will stop using oral contraceptives when planning a pregnancy and conceive within a few menstrual cycles.

The study also postulate that future research could examine the different formulations of oral contraceptives as other health outcomes, such as breast cancer risk have varied by formulation—with triphasic levonorgestrel formulations driving the increased breast cancer risk.

References:

http://www.webmd.com/sex/birth-control/news/20141211/the-pill-remains-most-common-method-of-birth-control-us-report-shows

http://www.cdc.gov/nchs/fastats/contraceptive.htm

http://www.uptodate.com/contents/hormonal-methods-of-birth-control-beyond-the-basics

http://www.bmj.com/content/352/bmj.h6712

Mosher WD, Jones J. Use of contraception in the United States: 1982-2008. Vital Health Stat 23 2010:1-44.

Skouby SO. Contraceptive use and behavior in the 21st century: a comprehensive study across five European countries. Eur J Contracept Reprod Health Care 2004;9:57-68.

http://prospect.rsc.org/blogs/cw/2011/01/11/my-hero-carl-djerassi/#more-6286

http://cebp.aacrjournals.org/content/19/10/2496