Fibroids Flashcards
(6 cards)
What are Uterine fibroids (leiomyomas)?
- Benign fibrous tumours in the smooth muscle layer of the uterus: increased proliferation of disordered smooth muscle cells
- Multiple Pathways involved: transforming growth factor-β (TGF-β), CD24 and insulin-like growth factor (IGF-1)…… ….responsiveness to oestrogen
- Tend to have multiple, range in size from a few millimetres to massive growths of 20cm diameter and more.
Locations
* Submucosal (intrauterine); Can interfere fertility issues as the endometrium around the
fibroid does not undergo normal hormonal change, affecting implantation. Preterm birth and the miscarriage rate is often higher.
* Intramural fibroids (within the muscle layer)
* Subserosal fibroids (extra uterine), under the serous outer lining. If pedunculated, extreme pain if torsion
What are the risk factors and signs and symptoms?
By age 50, 70% of women will have one or more uterine fibroids, higher incidence in black women.
Usually appear around the early 40s, (although could be asymptomatic earlier) 15 to 30% of women have symptoms and these depend partly on location.
Symptoms:
* Menorrhagia, leading to anaemia
* Pelvic discomfort, pressure symptoms (urinary incontinence and constipation). Heaviness in the lower abdomen, sensation ‘as though everything might fall out’ before or during the period, dysmenorrhoea.
Risk Factors
* Age: increasing incidence with age up to the menopause, then usually decreasing in size , which may be related to reduced oestrogen exposure.
* Early menarche: increased risk.
* Nulliparity: Epidemiologic data show
that pregnancy is associated with reduced risk of fibroids.
What is conventional diagnosis for fibroids?
Diagnosis
* Abdominal examination.
* Ultrasound.
* MRI may be used to delineate the number, size and location of fibroids
What part does oestrogen excess, obesity and growth factors play?
Oestrogen excess
* The enzyme aromatase in fibroids, which governs the conversion of androstenedione into estrone and testosterone into estradiol.
* Higher incidence is found in those suffering from other oestrogen excess conditions such as endometrial hyperplasia and endometriosis
* Oral contraceptives; as elevated risk of fibroids among women who used oral
contraceptives in their early teenage years (13-16 years of age) compared with those who had never used them.
* Hormone replacement therapy (HRT)
* Tamoxifen (antiestrogenic in breast tissue), estrogenic effects on the uterus and has been linked to fibroid growth in several clinical studies.
* Exposure to Environmental oestrogen; Fibroids contain larger amounts of DDT than other uterine tissue. DDT has oestrogen-like effects
Obesity
* Increased incidence of uterine fibroids.
* Obese premenopausal:
* Decreased metabolism of estradiol by the 2 hydroxylation route reduces the conversion of estradiol to inactive metabolites, which could result in a relatively hyperestrogenic state.
* 17 betahydroxysteroid dehydrogenase (17beta-HSD), which converts estrone into oestradiol (the active form of oestrogen) is overexpressed.
* Fat cells; conversion androgens to oestrogens.
Growth Factors
* Transforming growth factor-beta (TGF-beta) overexpressed in fibroid cells which is hormonally regulated.
* Prolactin is produced by uterine tissues as well as the pituitary gland; growth promoter for vascular smooth muscle.
What about injury, lifestyle or hypertension?
Abnormal response to injury hypothesis
* Menstruation causes vasoconstriction and hypoxia, and this ‘repeated injury’, activated myofibroblastic cells in fibroids.
* Infection: case-control study incidence of uterine fibroids was positively correlated with a history of pelvic infection.
Lifestyle:
Serum vitamin D levels correlated with fibroid size; fibroid volume correlated inversely with vitamin D in more so in African American women.
Smoking reduced risk (not past smoking), possibly related to antiestrogenic effect of cigarette smoking. Increased risk for more than 7 drinks of beer per week.
Chronic life stress; Could affect eating habits, and weight, and affect hormone levels.
Hypertension
* Fibroid incidence as well as risk of fibroid growth increases with high blood pressure.
* High-density lipids (HDLs): protective of atherosclerotic changes, lower in women with fibroids,
* Hypertension, damages the smooth muscle lining of the arteries, and atherosclerosis is in part a proliferative condition of blood vessel walls.
* Elevated blood pressure causes smooth muscle injury and/or secretion of cytokines (as in the pathogenesis of atherosclerosis)
What is conventional treatment for fibroids?
Conventional treatment
Asymptomatic fibroids do not require treatment.
Patients should be re-evaluated periodically (eg every 6 to 12 months).
Symptomatic fibroids, in perimenopausal women, management of symptoms, as usually symptoms may resolve as fibroids decrease in size after menopause.
* Drugs for temporary relief of minor symptoms
* Myomectomy or hysterectomy for symptomatic fibroids
* Drugs for fibroids; GnRH agonists to reduce size and bleeding, Exogenous progestins, Antiprogestins, Selective estrogen receptor modulators (SERMs), Danazol
* NSAIDs can be used to treat pain but probably do not decrease bleeding.
* Tranexamic acid (an antifibrinolytic drug) can reduce uterine bleeding
