MIT HST 071 - Human Reproductive Biology (5 pages)

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Human Reproductive Biology



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Human Reproductive Biology

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5
School:
Massachusetts Institute of Technology
Course:
Hst 071 - Human Reproductive Biology
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Harvard MIT Division of Health Sciences and Technology HST 071 Human Reproductive Biology Course Director Professor Henry Klapholz HST 071 IN SUMMARY FIBROIDS FIBROIDS Smooth muscle tumors of the uterus very common Occur in more than one third of women over the age of 35 Complaints include discharge bleeding from the vagina pain pressure Circumscribed but not truly encapsulated Tumor can be readily shelled out is glistening gray Composed of interdigitating bundles of smooth muscle Incidence in black women three times greater than in white women Strong hormonal relationship LOCATION Intramural subserosal and submucosal Subserosal and submucosal leiomyomas may become pedunculated Submucosal leiomyomas most important bleeding symptoms may occur May occur in the cervix and broad ligaments as well Few mitoses are present Their spindle shape is readily apparent When the cells are cut across the nuclei appear round Frequently undergo degeneration hyaline and cystic Presence of large amounts of connective tissue known as fibromyomas or fibroids Bleeding symptoms caused in part by thinning of the overlying endometrium Vessels are not capable of retracting in the usual manner No basal zone from which the overlying thin layer of endometrium can regenerate Submucous pedunculated leiomyomas may prolapse Necrosis in intramural leiomyomas Only one artery supplies the leiomyoma May calcify or undergo red degeneration ATYPICALITY Atypicalities occur in leiomyomas may be confused with leiomyosarcomas Mitotic rate is characteristically less than 5 per 10 high power fields Intravascular leiomyoma rare tumor nodular masses of histologically benign smooth muscle growing within veins INCIDENCE ETIOLOGY Most common solid pelvic tumors in women Clinically apparent in 20 to 25 of women during the reproductive years Pathologic inspection of the uterus present in more than 80 Leiomyomas are clonal in origin o Classic paradigm caused by and stimulated to grow by o Estrogen o Progesterone It is now clear that the following are responsible for fibroid growth o Transforming growth factor s o Basic fibroblast growth factor o Somatic mutations of genes such as HMGI C Fibroids are characterized by their location in the uterus o Subserosal leiomyomas o Intramural leiomyomas o Submucous leiomyomas Few leiomyomas are actually of a single pure type Most leiomyomas are hybrids that span more than one anatomic location Increased incidence of leiomyomas in women of color Risk is increased in women with greater body mass index Decreased in women who smoke or who have given birth IN SUMMARY FIBROIDS Good epidemiological evidence to suggest that use of oral contraceptive Birth control pills decreases the risk for leiomyomas 20 and 50 of women with leiomyomas have tumor related symptoms Fibroids often cause Abnormal uterine bleeding Prolonged menstrual flow menorrhagia Submucous leiomyomas appear to be particular ly prone Pelvic pressure Increase in uterine size Pressure of particular myomas on adjacent structures Colon constipation Bladder urinary frequency Ureters hydronephrosis Recurrent miscarriage Infertility Premature labor Fetal malpresentation Complications of labor HST 071 DIAGNOSIS Easily determined by bimanual examination Uterus is enlarged Mobile Irregular Palpated abdominally above the symphysis Ultrasonography most common method for diagnosis Submucous fibroid can be missed on traditional ultrasonography Magnetic resonance imaging MRI Electron spin characteristics can often distinguish Leiomyomas Adenomyomas Leiomyosarcomas Primary therapy for patients with large or symptomatic leiomyomas is surgery Hysterectomy is the most often United States more than 175 000 hysterectomies are performed yearly for leiomyomas o Diagnosis of leiomyoma the most common indication for this procedure o Hysterectomy the only true cure for leiomyoma is a surgical option when women are no longer interested in future pregnancies Subtraction angiography o Easily visualize the fibroids and also embolize them in order to cause infarction o May dramatically reduce bleeding as well as size Myomectomy o 18 000 myomectomies are performed yearly o Myomectomy diminishes menorrhagia in roughly 80 o Significant risk for recurrence of leiomyomas o Ultrasonography evidence of recurrence in 25 to 51 of patients o 10 require a second major operative procedure GnRH agonists Lupron Naferelin Gosserelin o Induce a hypo estrogenic pseudo menopausal state o Fibroids are dependent on estrogen for their development and growth o Hypo estrogenic state causes shrinkage o Uterine volume has been shown to decrease 40 to 60 after 3 months IN SUMMARY FIBROIDS o o o o HST 071 Induces amenorrhea increase iron stores and hemoglobin concentrations Cessation of GnRH agonist treatment results in rapid re growth GnRH agonist treatment is useful as a pre surgical treatment Not a long term treatment option Androgenic agents Danazol Gestrinone Progestins Medroxyprogesterone acetate Provera Depo medroxyprogesterone acetate Depo Provera Norethindrone Do not consistently decrease uterine or fibroid volume Mechanism of action is thought to be the induction of endometrial atrophy Often not successful in controlling significant menorrhagia Somatic mutation is the initial event in most tumorigenesis Somatic mutations include a variety of chromosomal aberrations Point mutations or Chromosomal loss or gain Large chromosomal abnormalities such as translocations and deletions often detected with standard cytogenetic karyotypes Independent monoclonal origin of individual myomas Suggests somatic mutations offer a selective growth advantage to the mutated myocyte Variety of chromosomal rearrangements Most common 12q14 15 and 7q22 Heterogeneity of the cytogenetic abnormalities Different somatic mutations may be involved in myoma tumorigenesis Unique somatic mutations in individual myomas Biologic basis for the differential responsiveness of individual myomas to a variety of growth promoting agents SOME THOUGHTS ON THE DEVELOPMENT OF FIBROIDS Clonal proliferation precedes the development of cytogenetic rearrangements o Somatic mutations which cannot be detected cytogenetically with the light microscope are the initial events in myoma tumorigenesis o Explains the absence of cytogenetic abnormalities in a large proportion of myoma specimens ER alpha and ER beta mRNA expressed in leiomyoma and normal myometrium Expression of ER alpha higher than ER beta in both leiomyoma myometrium ER


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