Secondary AMENORRHEA Presented by LINA ALHIARY 6 TH
Secondary AMENORRHEA Presented by LINA AL-HIARY 6 TH YR medical Student
Definition and Etiology OF Secondary Amenorrhea � Secondary means that menstrual bleeding had previously occurred so, Secondary amenorrhea is diagnosed with absence of menstruation for more than 6 months in a normal female of reproductive age that is not due to pregnancy, lactation or the menopause � There are multiple etiologies for secondary amenorrhea, which can be classified by alterations in FSH and LH levels. They include: 1. Hypogonadotropic (suggesting hypothalamic or pituitary dysfunction), 2. Hypergonadotropic (suggesting ovarian follicular failure), 3. and Eugonadotropic (suggesting pregnancy, anovulation, or uterine or outflow tract pathology).
Etiology OF Secondary Amenorrhea � Ovarian in origin 40% 1. Polycystic ovary syndrome (40%) 2. anovulation 3. Ovarian failure 4. Autoimmune oophoritis Hypothalamic in Origin 35% Hypothalamic disorders will give rise to hypogonadotrophic hypogonadism, with the following causes: 1. Excessive exercise, weight loss and stress. 2. Hypothalamic lesions (craniopharyngioma, glioma), which can compress hypothalamic tissue or block dopamine. 3. Head injuries. 4. Systemic disorders including sarcoidosis, tuberculosis resulting in an infiltrative process in the hypothalamo-hypophyseal region. 5. Drugs: progestogens, HRT or dopamine antagonists. �
�Pituitary in origin (20%) Pituitary disorders will also give rise to hypogonadotrophic hypogonadism, with the following causes: 1. Adenomas, of which prolactinoma is most common. 2. Pituitary necrosis (e. g. Sheehan’s syndrome, due to prolonged hypotension following major obstetric haemorrhage). 3. Iatrogenic damage (surgery or radiotherapy). � Uterine in origin (5%) Secondary amenorrhoea may result from scarring of the endometrium called Asherman syndrome � Severe systemic illness: Renal failure, Endocrine diseases( Hypothyroidism ) � Medications : Antipsychotic , Antdepressent, chemptherapy , radiotherapy , illicit drugs : cocaine , opiates
APPROACH TO SECONDARY AMENORRHEA � First step is taking HX doing P. E with Ruling out physiological cause: Pregnancy , Lactation and menopause. BY HX 1. AGE 2. Irregular menstrual cycles , infertility , Acne , Hirsutism – associated with PCOS 3. stress, change in weight, diet, or exercise habits, or illness- associated with hypothalamic amenorrhea 4. hot flashes , vaginal dryness , poor sleep , decreased libido - symptoms of estrogen deficiency 5. galactorrhoea – may be due to prolactinoma 6. Headaches, visual symptoms – may be suggestive of CNS tumor 7. H/O postpartum hemorrhage – may be associated with Sheehans syndrome 8. H/O dilataion and curretage – may be associated with Ashermans syndrome 9. Drugs: Contraception, antidepressants and antipsychotics, Chemotherapy 10. H/O of Chronic diseases: Thyroid diseases, sarcoidosis , ….
PHYSICAL EXAMINATION � General Weight, height, body mass index (BMI) Blood pressure, thyroid exam 1. BMI greater than 30 -PCOS. 2. BMI less than 18. 5 kg/m 2 may have functional hypothalamic. � The patient should be examined for hirsutism, acne, striae, acanthosis nigricans, � Breasts should be examined for evidence of galactorrhea. � Vulvovaginal exam should look for signs of estrogen deficiency. � Abdomen/pelvis Mass arising from pelvis
Inevestigation and Treatment �Pregnancy Test. The first step in evaluation of secondary amenorrhea is to obtain a qualitative β-h. CG test to rule out pregnancy �Thyrotropin (TSH) Level. If the β-h. CG test is negative, hypothyroidism should be ruled out (TSH level). The elevated thyrotropinreleasing hormone (TRH) in primary hypothyroidism can lead to an elevated prolactin. If hypothyroidism is found, treatment is thyroid replacement with rapid restoration of menstruation �Serum prolactin Levels. If elevated , the cause must be identified 1. antipsychotic medications or antidepressants. 2. A pituitary tumor should be ruled out with CT scan or MRI of the brain. If a pituitary tumor is found and is< 1 cm, treat medically with bromocriptine , If >1 cm treat surgically. 3. Idiopathic. If the cause of elevated prolactin is idiopathic, treatment is medical with bromocriptine
�FSH & LH, Testosterone, DEHA levels If PCOS –treat accordingly (next slides) A high serum FSH concentration indicates primary ovarian insufficiency (premature ovarian failure) Progesterone Challenge Test (PCT). If the β-h. CG is negative, and TSH and prolactin levels are normal, administer either a single IM dose of progesterone or seven days of oral medroxyprogesterone acetate (MPA). 1 -Positive PCT. Any degree of withdrawal bleeding is diagnostic of anovulation. • Cyclic MPA is required to prevent endometrial hyperplasia. • Clomiphene ovulation induction will be required if pregnancy is desired. 2 -Negative PCT. Absence of withdrawal bleeding is caused by either • inadequate estrogen priming of the endometrium or • outflow tract obstruction such as cervical stenosis or uterine synechiae (Asherman's syndrome).
� Estrogen–Progesterone Challenge Test (EPCT). If the PCT is negative, administer 21 days of oral estrogen followed by 7 days of MPA. 1 -Positive EPCT. Any degree of withdrawal bleeding is diagnostic of inadequate estrogen. An FSH level will help identify the etiology. 1. Elevated FSH suggests ovarian failure. If this occurs age before age of 30 yrs – order karypotype 2. Low FSH suggests hypothalamic–pituitary insufficiency. Order a CNS imaging study to rule out a brain tumor. Whatever the result, women with a positive EPCT( such as premature ovarian failure ) will need estrogen-replacement therapy to prevent osteoporosis and estrogen-deficiency morbidity. Cyclic progestins are also required to prevent endometrial hyperplasia If Sheehan's syndrome is diagnosed, treatments will be lifelong hormone replacement therapy which may include corticosteroids oestrogen and Levothyroxine. 2 -Negative EPCT. Absence of withdrawal bleeding is diagnostic of either 1. an outflow tract obstruction (as cervical stenosis treated by hystroscopy and cervical dilations ) endometrial scarring (e. g. , Asherman syndrome). A hysterosalpingogram (HSG) will identify where the lesion is. Asherman is treated by hysteroscopic adhesion lysis followed by estrogen stimulation of the endometrium. An 2.
�PCOS , also called Stein leventhal syndrome �A condition of chronic anovulation resulting in subfertility, irregular bleeding, and Hyperandrogenism . Other symptoms include obesity , Acne and hirsutism. �It's a common condition affecting 5 -10 % of females in reproductive age.
�The aetiology of PCOS is not completely clear, a and is thought to have a multifactorial etiology. Although there is a genetic component, the manifestation of the syndrome is influenced by nonhereditary factors as well. �The prevalence of PCOS among first-degree relatives appears to be between 35% and 40%. �Insulin resistance among family members of patients with PCOS also appears to be significantly greater than that of the general
� Chronic anovulation. Instead of showing the characteristic hormone fluctuation of the normal menstrual cycle, in PCOS gonadotropins and sex steroids are in a steady state, resulting in anovulation and infertility. Without ovulation, there is no corpus luteum to produce progesterone. Without progesterone, there is unopposed estrogen. Endometrium, which is chronically stimulated by estrogen, without progesterone ripening and cyclic shedding becomes hyperplastic with irregular bleeding. With time endometrial hyperplasia can result, which could progress to endometrial cancer Increased luteinizing hormone and testosterone : LH stimulates production of androgens from theca cells in the ovary. Normally, androgens in the ovary are converted to estrogens in the granulosa cells. In women with PCOS, increased LH results in increased follicular theca cell production of androgens. The increased levels of androstenedione and testosterone suppress hepatic production of SHBG by 50%. The combined effect of increased total testosterone and decreased SHBG leads to mildly elevated levels of free
� Abnormal Gn. RH secretion: is a result of the lack of the feedback mechanism because of the low progesterone levels or an intrinsic defect in Gn. RH pulse generator � Insulin resistance: metabolic pathway of insulin activity is defective, whereas the activation of steroidogenesis is maintained 1. Insulin directly stimulates production of androgens from theca cells by binding to its receptor. 2. Insulin also decreases the production of sex hormone-binding globulin (SHBG) produced by the liver. This in turn decreases the amount of testosterone bound to SHBG and therefore increases the free metabolically active testosterone.
� Amenorrhea or oligomenorrhea in 75% of the patient, predominantly related to chronic anovulation. � Hirsutism � Alopecia (thining of hair ) � Acne � Depression and other mood disorder � Subfertility in up to 75% of women � Insulin resistance acanthosis nigricans and hyperinsulinemia obesity and type 2 diabetes • May be asymptomatic.
�Rotterdam criteria: Two out of three of the following to make a diagnosis (after ruling out CAD, androgen-secreting tumors & Cushing syndrome): Ovulatory dysfunction • 75% will have oligomenorrhea/Amenorrhea • Reminder will have normal menses (check ovulation by measuring progesterine level in mid luteal phase Evidence of Hyperandrogenism • Clinical : Hirsutism , Acne • Biochemical : Testosterone is mildly elevated <5 nmol/l and SHBG will be decreased POLYCYSTIC OVARY ON US • The ultrasound critreria for the diagnosis of a polycystic ovary are eight or more subcapsular follicular cysts < 1 o mm in diameter and increased ovarian stroma
Adams criteria • > 12 follicles in one plane Sized 2 -9 mm • Dense stroma • Ovarian volume > 10 ml or ovarian area >5. 5 cm square While these findings support a diagnosis of PCOS, they are not by themselves sufficient to identify the syndrome.
� Diabetes: Impaired glucose tolerance is diagnosed by a 2 -hour glucose tolerance test � Obesity: Most often truncal with an android appearance and an increased waist-to-hip ratio and it is related to insulin resistance � Endometrial hyperplasia: Chronic anovulation exposes the endometrium to unopposed estrogen, which increases the risk of endometrial hyperplasia which can progress to endometrial cancer if left untreated � Cardiovascular disease: Increased risk for hypertension, dyslipidemia, and glucose abnormalities (Metabolic Syndrome) � Infertility
�A 25 -year-old morbidly obese African American female, married, gravida 0, who presented to the gynecology office for evaluation of irregular menses since menarche. She has on average 2 period every 6 months. When she does have her period, she bleeds very heavily, passing large clots. She also complained of excessive facial hair, which requires her to shave and a lot of hair on her abdomen and arms. She denied any change in her voice or increase in the size of her muscles. No hyper/hypothyroid symptoms. She has never conceived, despite several years of trying.
�On Examination: 1. -Ferriman-Gallowey score of 2. 3. 4. 5. 10: especially in the chin and midabdominal regions. -BMI=32 kg/m 2 -No evidence for clitoromegaly -Her uterus and adnexa were very difficult to assess secondary to the patient's morbid obesity -The rest of her physical exam was unremarkable
Lab Tests: 1. -FSH was normal, but LH was elevated. Elevated LH to FSH ratio (3: 1) (normal in ovulatory pt is 1. 5: 1) 2. -TSH, prolactin, chemistry panel, were all within normal limits. 3. -Fasting blood sugar was 130 mg/d. L, and the 2 -hour value on glucose tolerance test was 233 mg/d. L. 4. -ELEVATED LDL , Triglycerides levels , LOW HDL 5. -Total testosterone and free testosterone were elevated. 17 OHprogesterone & DHEAS were normal. 6. 5 -Endometrial aspirate showed proliferative endometrium without hyperplasia or neoplasia. On Ultrasound: Normal appearing uterus, and polycystic ovaries.
1 -Lifestyle changes Weight Reduction : 2. Regular exercise , 3. good hydration, 4. healthy eating plan (high protein, low carbohydrate) all help in improvement of insulin sensitivity Research has shown that weight loss of 5– 10% of initial body weight in women who are obese can significantly improve symptoms of PCOS and may improve the chance of pregnancy 1. 2 -Medications � Oral contraceptives: Control androgen excess by increasing SHBG, regulate periods and painful periods & minimizes endometrial hyperplasia or cancer. � Metformin: decrease insulin resistance, helps in losing weight and enhances ovulation. � Antiandrogens: Spironolactone is used as a product for acne vulgaris owing to its antiandrogen-acting properties, finasteride and flutamide, can be used for hirsutism. � Clomiphene citrate: Induces ovulation where subfertility is a factor � Assisted Reproductive
� Hirsutism can be suppressed two ways: OCPs will (a) lower testosterone production by suppressing LH stimulation of the ovarian follicle theca cells, and (b) increase SHBG (thus decreasing free testosterone). Spironolactone suppresses hair follicle 5 -α reductase enzyme conversion of androstenedione and testosterone to the more potent dihydrotestosterone. Also Eflornithine cream (Vaniqua™) applied topically. � Ovarian drilling, a laparoscopic procedure to destroy some of the ovarian stroma that may prompt ovulatory cycles. � surgical treatments (e. g. laser or electrolysis).
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