Uterine fibroids are estrogen-dependent benign tumors that arise from uterine smooth muscle and fibrous connective elements contain. The correct name is the leiomyoma but also is designated with the names of myoma, fibroma, fibro-myoma and fibroid. May have different sizes and must be unique or, more frequently, multiple. It is difficult to pinpoint the actual incidence of myoma, as often is symptomatic. In the general population is 1 in 4 women in active reproductive age, has been detected in autopsies in 50% of the uteri. Fibroids are also one of the most common causes of infertility in women. 40% of hysterectomies (excision of the uterus) are performed as a treatment for uterine fibroid uterine. Hysterectomy is surgery unrelated to pregnancy more common in women. Occasionally not offer alternatives to many women with fibroids than hysterectomy. This can be critical if the woman is in her reproductive years and wish to become pregnant. For such patients, in most cases, there is the option of myomectomy, which involves removing the fibroids, while respecting the uterus, which often have to rebuild


Role of ovarian steroids: Ovarian steroids appear to be involved in increasing leiomyoma size while preserving their differentiation while maintaining its benign activity.  Both estrogen and progesterone are actively involved in the increase in size of leiomyomas abnormally stimulating the expression of autocrine growth factors and paracrine. It is proven that almost 50% of fibroids have an increased mitotic activity during the luteal phase of the cycle, while remaining relatively inactive during the follicular phase. The term benign can not really be applied to certain leiomyomas during the luteal phase exhibit reach 40 or more mitotic figures per 100 high power fields. These are called "tumors of unknown malignant potential. Mitotic activity is higher in young women aged between 30 and 35 who may be relatively small compared with tumors between the ages of 45 and 55. In the myometrium during the menstrual cycle, estrogen receptors increase progressively until the mid-luteal phase and then decrease probably due to high levels of progesterone. In the myomas, the synthesis of estrogen receptors during the first phase of the cycle in which estrogen is elevated without opposition from progesterone.


Estrogen, on the other hand, is actively involved in the increased size of fibroids. The induction of a state hypoestrogenic is associated with a decrease in tumor volume of approximately 50%. Treatment with agonists Gn-RH significantly reduces the volume of the myometrium which shows how leiomyomas respond the same way as normal tissue when steroid levels are altered. The increased number of mitosis in leiomyomas during the luteal phase is a clear indication of mitogenic role of progesterone. Both in vivo and in vitro is a significant increase in mitotic activity is greater in women treated with progesterone than in those treated with estrogen-progestin or women not treated with steroids. It appears that progesterone and estrogen is not mitogenic hormone naturally in leiomyomas and in treatment with a progesterone antagonist such as RU 486 has proven to be as effective as similar treatment with the Gn-RH.  Thus, progesterone appears to act by raising the expression or altering the function of growth factors and their specific receptors. At one point, the elevation of these factors, receptors or alteration of its function would be more significant during the luteal phase when the mitotic activity of leiomyomas is higher. Expression of growth factors, hormones and their receptors in leiomyomas autocrine and paracrine systems regulate cell proliferation and organ development through local production of growth factors and hormones. Without the proper receptor, no cell reacts to a hormone or growth factor determined independently of its blood level. The epidermal growth factor (EGF) has a mitogenic activity on both the ovary and the endometrium. Production of EGF appears to be one mechanism through which progesterone stimulates mitotic activity in leiomyomas during the luteal phase.


The insulin growth factor (IGF-I) binds to its specific receptor exerting a mitogenic effect on both the ovary and the endometrium. However, the importance of IGF-I in leiomyoma growth is obscured by the fact overexpression of this factor and its receptor during the follicular phase when leiomyomas have the lowest mitotic activity. The rate of rise of IGF-I during the late follicular phase suggests the possibility that actu primo tumor cells to further increase the mitotic activity in the luteal phase. Other growth factors like IGF-II, PDGF, and so on. play a complementary role or allowance for modulating tumor cells.


Prolactin (PRL) is another potential mitogen controversial role in the development of leiomyomas. Both the myometrium and leiomyomas produce PRL in response to human chorionic gonadotropin (HCG). However, the significance of production in the leiomyoma is unclear despite the recent identification of the expression of its receptor (5). The inhibition of PRL production in the leiomyoma by progesterone, suggests that this hormone is inhibited during the luteal phase when they are mitotically active leiomyomas. Leiomyomas also contain specific receptors for different polypeptides produced by other tissues such as growth hormone and insulin. The effects of growth hormone (GH) are numerous and are mediated by increased estrogen receptors in the uterus. The presence of GH receptors in leiomyoma and surrounding myometrium, opens the possibility for the role of GH in the development of leiomyomas directly or synergistically with progesterone. Insulin, which stimulates DNA synthesis in the myometrium and leiomyomas cells, act favoring the effect of EGF on the growth of leiomyoma in the luteal phase.


Role of cytokines


Little is known about the effect of quote machines on the fibroid tumors. One of the most studied families for the group of TGFb (transforming-growth factor), multifunctional polypeptides that have a profound effect on cell differentiation. They are structurally similar to inhibin and Mullerin inhibiting substance (MIS). They share the same inhibitory activity on growth by blocking the mitogenic action of EGF, TGF? and interleukin-2. The TGFb is considered a suppressor gene because of its antiproliferative action that exceeds the action of mitogens. The expression of TGFb is regulated by ovarian steroids. The highest levels appear in the follicular phase and late luteal phase start to decrease at the end of it, suggesting that TGFb is stimulated by estrogen and inhibited by progesterone in human uterine tissue. It can also inhibit mitogenic activity of IGF-I and IGF-II during the follicular phase. Finally, TGFb stimulates extracellular matrix formation by accelerating the incorporation of fibronectin and collagen production and inducing related peptide parathyroid hormone (PTHP) (7). This peptide regulates the flow of calcium into the cell and has been shown elevated in leiomyoma and menstrual cycle during the follicular phase. The extracellular content of leiomyomas suggests that TGFb plays an active role in their development by stimulating the expression of extracellular matrix components during the follicular phase. The reality is that this attractive hypothesis remains to be investigated because the role of TGFb in the development of leiomyomas remains obscure.


Pathology of Leiomyomas


Leiomyomas arise from the myometrium, the uterine intramural area, from a single clone of smooth muscle cells, with the continued growth in one direction. The location may vary in relation to the myometrium. Definition: Fibroids are benign (not cancerous), most common female genital tract. Fibroids are a hardness of uterine muscle, which is produced by the abnormal growth of cells in the matrix. Are round, firm and elastic. May be single or multiple and of varying size are also known as fibroids, fibroids or leiomyomas. They develop in the muscular wall of the uterus. Although not always produce symptoms, size and location can cause problems in some women, such as major bleeding and pelvic pain in the lower abdomen. Although the exact causes of the occurrence of fibroids are not yet well established, researchers believe that owe as much to a genetic predisposition to greater sensitivity to hormonal stimulation (mainly estrogen). Some women can have this predisposition, develop factors that allow these to grow under the influence of female hormones. Reason would explain why certain ethnic groups and families are more likely to have fibroids. Fibroids vary greatly in size. In some cases, can cause a marked growth of the uterus, simulating a pregnancy up to 5 or 6 months. In most cases, fibroids are multiple.


Macroscopic description:  Fibroids may be located in various parts of the uterus. There are basically three types of fibroid:


1. Submucosal myoma

2. Intramural Fibroids

3. Subserosal myomas


1 Subserosal: They appear and develop under the layer (serosa) outside the uterus and spread through it, giving a nodular appearance to the uterus. Typically not affect menstrual flow, but can cause lower abdominal pain in the lumbar region and pressure sensation in the abdomen. They often develop a belaying pin or pedicle, making them difficult to distinguish from an ovarian tumor on ultrasonography.


2 - Intramural: They develop in the uterine wall and extend inward, increasing the size of the uterus. They are the most common type of fibroid. They can cause heavy menstrual bleeding and pain in the lower abdomen and lower back and / or general feeling of pressure in the lower abdomen, that many women complain.


3 - Submucosal: We found just under the lining of the uterus (endometrium). Although less common is the type of myoma, are most often causes problems. Even a small submucosal fibroid can cause massive bleeding gynecological. They are more symptomatic lesions; originate from the myometrial wall and protrude into the endometrial cavity. Submucosal fibroids may be suspended by a pedicle and even prolapse through the cervical os (myoma calved).


4 - Pedicle: These fibroids grow initially as subserosal and highlights part of the uterus, being connected to it only by a small piece of tissue called the pedicle. They can confuse with ovarian ultrasonography


Common Symptoms


Most fibroids have no symptoms - just the 10 to 20% of women who have fibroids require treatment. Depending on their location, size and quantity, the woman may experience the following symptoms: Prolonged periods and with increased flow, bleeding out of time, sometimes clots, and anemia. These are symptoms frequently associated with fibroids. Additionally, you can check:   Increased intensity of menstrual cramps.  Pain in the lower abdomen, or more accurately, feeling of pressure or discomfort caused by the size and weight of fibroids that press on adjacent structures. Pelvic pain, mass effect on the urinary bladder, increasing the frequency, mass effect on the rectum causing constipation, tightness and pelvic pain during intercourse. Pain in the lumbar region, lateral abdomen or legs (fibroids may press on the nerves that pass through the lower abdomen and legs).  Pain during sexual intercourse. Pressure on the urinary system, which always results in an increased frequency of urination, especially at night. Pressure in the large intestine, leading to constipation and gas retention. Increased abdominal size which can be misinterpreted as progressive weight increase.


Fibroids are very common tumors. The number of women who have fibroids increases with age until menopause, when then they are diminished by lack of hormonal stimulation. Approximately 20% of women with fibroids between 20 and 30 years, 30% between 30 and 40, and 50% between 40 and 50. From 20 to 40% of women 35 and older have fibroids of significant size. Women of color have a higher risk for fibroids: 50% may have fibroids of significant size. No one knows for sure why, although there appears to be a genetic factor play an important role. While fibroids can appear in women at age 20, most women have no symptoms until 30-40 years. Doctors are unable to predict if a fibroid will grow or cause symptoms. Fibroids are almost always improve after menopause, when hormone levels drop enough, although this is not always true.


Degenerative changes

If the fibroid is growing in excess in proportion to its blood supply, tumors can undergo degeneration processes:


  • 1.-Hyaline degeneration: It is found in 65% of fibroids in varying degrees. The tissue loses the typical pattern and presents a homogeneous and soft consistency to be replaced by smooth muscle cell tissue.


  • 2.-Cystic degeneration: Liquefy hyalinized zones, cavities can be formed true liquid of varying size, occurring in 4% of fibroids.


  • 3 .- Myxomatous degeneration: Present in 15% of the leiomyoma.


  • 4 .-. Degeneration of calcification: In 4-10% of cases, most commonly in older women (postmenopausal), is common in pedunculated subserosal fibroids, requiring poor vascularization. Histologically calcium deposits appear on slides.


  • 5.-Fatty degeneration: In advanced stages of hyaline degeneration, is rare.


  • 6 .- Necrosis: For lack of blood supply or extensive infection, may be focal or spread throughout the tumor, usually appear on other types of degeneration. Macroscopically myoma shows a soft yellowish-white. A very typical of necrosis or degeneration is the fleshy red, which occurs when the fibroid grows rapidly, there is a heart muscle that causes acute severe pain and localized peritoneal irritation. This form of necrosis is common during the second trimester of pregnancy. Fibroids may become infected secondarily necrotic, is more common in submucosal tumors after abortions, childbirth or uterine curettage.


  • 7 .- Malignant or sarcomatous degeneration: 0.5% of cases. The malignancy of a myoma is very rare. It is important to consider the possibility of existence of foci of cytologic abnormalities in the periphery of areas of necrosis, especially during pregnancy and in women receiving hormone treatment, which should not be confused with malignant foci. The existence of multiple cases of fibroids located not only in the uterus but also in the peritoneal surface and omentum. This syndrome is called disseminated peritoneal leiomyomatosis, there are very few reported cases.


Associated injuries


Leiomyomas are associated with relative frequency of glandular hyperplasia and cystic ovaries polimicroquísticos to areas of atrophic endometrium coexisting with areas of hyperplasia. Likely to influence a number of other factors besides hormones, such as the mechanic. Clinical forms, asymptomatic: The 50-80% of cases. Scans or additional clinical routines guide the diagnosis. Symptomatically: Pain torsion, cervical dilation (myoma calved), degeneration, etc. Uterine bleeding (62%) in the form menorrhagia or hypermenorrhagia by: Increased uterine size exceeding 200 cm. Decreased uterine contractility. Increased injury: inflammatory endometritis. Metrorrhagia associated with endometrial hyperplasia, endometrial atrophy anovulatory cycles. Increased abdominal circumference or volume. Urethral dysfunction or bladder compression.


Sometimes there are cases of polycythemia associated with uterine fibroids that do not correspond with the severity of uterine bleeding, this box is called "miomatosa erythrocytosis syndrome" (8) and resolves after hysterectomy.


Methods of Diagnosis


The effective use of imaging techniques has been reviewed recently.


Ultrasound: They serve to clarify the nature of the pelvic mass and allow, with a confidence of 80%, the differential diagnosis of a pregnancy, ovarian mass, or solid subserous myoma. Difficulties arise in differentiating between the myoma pedicle and solid ovarian tumor. Transvaginal ultrasonography (USV) helps us to differentiate and identify small intramural fibroids, submucosal often the most easily diagnosed by the vaginal route. Fibroids are seen in ultrasound as echodense defects within the myometrium, causing typically so dense distal shadow. Since the USV can only penetrate 5 cm. beyond the transducer, fibroids over this distance is best detected by abdominal ultrasonography (U.S.). Furthermore, USV has the advantage of visualizing the relationship of the myoma with the endometrial cavity, hence the rationale for their use. In the era of ultrasound, it is not appropriate symptomatic fibroids removed based on dimensional criteria, since you can monitor the growth and well-observed appendages. The sensitivity and specificity of diagnosis of submucosal fibroids using USV is nearly 90% so it is essential before hysteroscopic removal thereof.


Nuclear Magnetic Resonance Scan: It is of considerable value in demonstrating the nature of the pelvic mass, although the technique is very expensive and not widely effective, compared with ultrasound, it is more accurate in predicting the histological characteristics of a tumor. It is useful for research or in cases of diagnostic difficulty, for its high level of accuracy, but is not necessary in the routine management of fibroids.


Laparoscopy: Its use is valuable in the case of fibroids not beyond 12 weeks in size, with or without infertility or pelvic pain, and you can reveal the concomitant existence of endometriosis, pelvic adhesions or other tubal pathology. In case of doubt by ultrasonography, a pedunculated fibroid will differentiate us in a solid adnexal mass, and we provide the possibility of removing small fibroids.


Hysterosalpingography and hysteroscopy: One of these two procedures should be performed in cases of repeated abortions. The visualization of submucous myomas, investigating their size and location, can guide us in terms of implementation difficulty ovulating, or which exceeds the limits of the tubal ostium, causing obstruction. It is now increasingly being used to the existence of abnormal uterine bleeding (HUA). It has been shown that hysteroscopic submucous myomas were visualized in 13% of these patients, in addition, it allows selective biopsy. However, its use is not appropriate in cases of bleeding associated with large fibroids, where there will be a hysterectomy or myomectomy.


Treatment of uterine myomas

Although treatment is primarily surgical, however, in some cases can and should adopt a conservative attitude.


Watchful waiting: Several circumstances may be to which we owe to abstain to verify any treatment: Small and asymptomatic leiomyomas. Provided the diagnosis is secure, remain asymptomatic, and also regular checks to verify the woman (every 3-6 months) and must escape this watchful waiting if the fibroid grows or becomes symptomatic. Although traditionally has advocated the removal when the myoma size beyond 12 weeks gestation. A special case is the patient who consulted for infertility and discovers a small and symptomatic fibroid in the interstitial portion of the tube, which can hinder conception. The proximity of menopause for small and asymptomatic fibroids. During pregnancy Only in extreme cases (pedunculated fibroid with signs of acute abdomen) would be given a laparotomy followed by myomectomy.


Medical Treatment should accomplish two goals:


  1. Relief of symptoms (menorrhagia).


  1. Reduction in tumor size.


The ideal of all medical treatment should be complete tumor regression, but to date this has not been described, which is why medical treatments in the past have had a limited role in the management of fibroids. However, with recent advances in diagnosis and treatment techniques has been given importance, both as symptomatic treatment of fibroids as an adjuvant in surgery.


Progestogens: They are widely used in the treatment of HUD, but are generally regarded as ineffective in menorrhagia secondary to myoma. However they may be especially indicated in perimenopausal patients with fibroids, if the bleeding is due to anovulatory dysfunction, rather than a direct result of myoma. There is also evidence that progestins produce an alteration of the size of the fibroid, but Star Rihanna changes have been reported after administration of high doses of AMP.Androgens (danazol and gestrinone)


They are used in these cases to:


  1. Reducing or abolishing the menstrual loss in patients with menorrhagia, under the direct effect on the endometrium and inhibition of negative feedback of pituitary gonadotropin secretion.


  1. Relative decrease of 20% of fibroid volume.


  1. These agents may be beneficial in the short time in relieving symptoms, but long use, given its androgenic effects and collateral, make them unsuitable.


Inhibitors of the synthesis of prostaglandins (PG)


Likewise have been reported beneficial effects in the treatment of HUD, but not in the treatment of menorrhagia due to fibroids. However you can use in relieving pelvic pain in women with fibroids, including pain from degeneration of it.


Combination of estrogen and progesterone


A.C.O. (Oral contraceptives) Activate the development of fibroid? BARAZZINI (1992) has shown no growth and reduced risk. The A.C.O. their current degree not favor tumor development, although, in symptomatic fibroids treatment outcomes are not optimistic.


Hormone replacement Therapy : As for your role in myoma is not, as in the case of ACO, very clear increase in the volume of the fibroid, but this has not been confirmed in recent studies when using estrogen and progestin in small doses added to the GnRH analogues.


Progesterone antagonists: The application of GnRH antagonists has shown a rapid involution of fibroids in the same proportion and more rapidly than that obtained with GnRH analogues. In this regard recent work done shows the decrease in fibroid volume when administered at doses of 25-50 mg / day of a continuing form of opening an avenue of future prospects in the medical treatment of uterine myoma. The growth of fibroids is dependent on steroids and have an aggregate content of Estrogen Receptor (ER) and progesterone receptor (PR) compared with surrounding myometrium, is admissible, that the fibroids can be changed by the antiprogesterone.


Other authors have done with different doses, identical controls with the following findings:


  1. 4 weeks of treatment


  1. 8 weeks of treatment


  1. 12 weeks of treatment


These results were achieved with both 25 and 50 mg / day. We obtained 100% of amenorrhoea  It is intended to increase LH and androstenedione and testosterone decline, without hirsutism.


Adverse effects


  1. Mild hot flashes.


  1. Increased transaminases.


Confronting analogs showed little benefit. It is not elucidate the mechanism of action of RU 486 to decrease the growth of leiomyomas. GN RH analogues: They were first used in 1983 by Filicori and Shaw. Its mechanism of action would be:

  1. Abolition of the hypothalamic-pituitary function or disappearance of the secretion of FSH, LH, estradiol and fall of the figures are similar to the determinations in women castrated. This mechanism results in reduction of fibroids, an effect that will persist for the duration of GnRH analogue administration, the ending of it leads to rapid acquisition of its former size.


  1. Decreased tumor vascularization or reduction in uterine artery flow demonstrated by Doppler studies.


Its use will also provide minimal intraoperative hemorrhage loss, by providing the laparoscopic intervention and of course, conservative surgery, the integrity of the uterine cavity.  You can use goserelin (3.6 mg / day), buserelin (3.75 mg / day), triptorelin, leuprorelin, etc.


Directions: In the case of uterine fibroid uterine size can be reduced from 30 to 70% by decreasing local growth factor.  But the fact of its transient effect (tumor shrinkage), the effects of osteoporotic hipoestronism or suppression of ovarian function, as well as bleeding complications from degeneration in submucosal locations, make GN RH analogues are used for short time, and it preferably as an adjunct to surgery. You can also use this therapy to alleviate the anemia, along with other therapies, in severe cases of metrorrhagia, before application of a surgical method (hysteroscopic myomectomy or hysterectomy) during the previous three months.  In cases where the patient refuses or has contraindications to surgery, age or approaching menopause, can be used GnRH analogues associated with HRT: estrogen-progestin therapy. This will improve the symptoms of menopause, hot flashes, with increased bone mineral density (BMD), without causing excess menstrual disorders.


Vaginal Abdominal hysterectomy


In an interesting study published in Surgical Medical Encyclopedia discusses various retrospective collections based on the results of the piece, which show an excess of surgical indications in 50% of the interventions, because there was no histological injury. It follows that 6% were inappropriate. It has achieved a decrease of 33% with the advent of medical treatment and other surgical procedures. Whatever the type of hysterectomy, preoperative evaluation is the conventional gynecological any formal intervention. Preoperative antibiotics were made and thromboprophylaxis in patients at risk.


Vaginal hysterectomy


Indicated when the size of the viscera allow vaginal extraction. This pathway is contraindicated in the following cases:


1. Suspected adnexal pathology.


2. Faced with limited size, lack of vaginal operative experience.


3. Pelvic surgery and chronic inflammatory processes in pelvis minor.


If removal can not be continued, even though they experienced vaginal, and we should not hesitate to resort to hysterectomy. Intraoperative myomectomy is always intracapsular dissection of myoma and it provides no risk and can proceed to the partial fragmentation to achieve adequate mobility.


Abdominal Hysterectomy


  1. Infraumbilical laparotomy on previous incisions.


  1. Significant adnexal pathology.


  1. Bulky fibroids.


  1. Pfannenstiel incision.


  1. Total abdominal hysterectomy with double oophorectomy.


  1. After the menopause.


  1. Bilateral adnexal pathology.


Keeping annexed


  • Between 45 and menopause, family history decision as ovarian pathology, macroscopic aspects and risks of using HRT.


  • If you want to or can only retain an outbuilding / ovary, provided the right.


Ovarian vascularization seriously compromised after this time should carefully guard trying to be generous in allowing for its unusual broad ligament vasculature.


Subtotal Hysterectomy


There must be proposed:


  1. Risk of subsequent pathology despite surveillance.


  1. Does not prevent vaginal prolapse.


  1. Does not promote orgasm.


  1. Is acceptable only because of technical difficulties.


Associated disease


  1. Multiple fibroids.
  2. Myomectomy after operative field to facilitate, any increase in intraoperative bleeding.
  3. Broad ligament myoma.
  4. Myoma of the cervix.
  5. Adnexal pathology.


Either unilateral or bilateral bulky cysts either by tubal inflammatory disease. In both cases the surgeon must be extremely careful of both the multiple fibroids and in the adnexal pathologies, the mastery of technique makes it less likely intrafascial injuries.


Laparoscopy Hysterectomy


Vaginal hysterectomy / abdominal pain, assisted or carried out entirely by laparoscopy, is in full development period, but published series does not appear that the fibroid is one of its clearest indications. The association of myomas with adnexal pathology, as well as vaginal surgery problems associated with perineal, laparoscopic assistance is a priority to take into account.

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