Secondary Amenorrhea

1. Secondary Amenorrhea Dr. Sharon D. Rasquinha

2. Secondary Amenorrhea Defined as amenorrhea of 6 months or more in a woman with previous normal menstrual patterns in absence of pregnancy and lactation. In clinical practice patients rule advice earlier and it is prudent to begin with simpler investigations, reassurance and await the outcome. Physiological - Pregnancy Lactation

3. Pathological A. Uterine factors 1. Tubercular endometritis: Destruction of endometrium or inhibition of ovarian function by tubercular domin 2. Uterine Synchiae (Asherman’s syndrome) Intrauterine adhesions  viscerocortical reflex – amenorrhea Occurs following excessive curettage, infection or endometrial Hb. 3. Post radiation : Destruction of endometrium

4. 4. Surgical removal : Ablation of endometerium by laser, resutoscope 5. Acquired Obstruction (Gynatresia) of cervical canal causing serve stenosis or atresia following slectrocauterization, chemical burns and cervical amputation in fothergills repair operation, following conisation for cervical depplasia or C/N and genital tb 6. VVF – Cause unknown

5. B. Ovarian causes:Pre Ovarian failure : Absent or accelerated follicles • Chromosomal Etiology : Sex chromosome disorders • Fragile X Carriers [ 4-5%] • 2. Iatrogenic Causes: Early loss of follicle • radiation : dose of 800 cGy causes sterility • Pelvic radiation – makes the ovaries unresponsive do gonadotropins • Chemotherapy – Cyclophyosphamide • Surgical alteration of ovarian blood supply

6. Infections mumps premature ovarian failure Lubo- ovarian abscess seen in the absence of surgical treatment  follicular destructions and premature ovarian failure - - - - Point 3 is missing - check 4. Autoimmune disorders ovarian failure may be a part of olyglanduylar autoimmune syndrome (Antibodies are present in a variable number of patients with premature ovarian failure Myasthemiagraries, 17P, RP, vitiligo, autoimmune hemolytic anemia, diabetes mellitus and others.

7. 5. Glactosemia (mild form and heteozygote) 6. Savage syndrome: follicles are present but resistant do gonadrotropins (FSH receptor defect) 7. Idiopathic 8. Cigarette Smoking : inverse dose – response relation with age of menopause increase the risk of diminished ovarian reserve alter both gamesomeness and hormonogenesis suggest an effect on follicle.

8. 9. Subtosomal gene mutations AR form POF – • II PCOS: Domically elerated LH  androgen production form theca cells and stroma of the ovaries  decreased SHBG  increased unbound estrogens and androgens – pituitary sensitivity do GnRh is increased H and  FSH due to inhibit disturbed adrenal function is also implicated in androgen excess. • Hyperestrogenic state: The estrogen heal remains high and there is no fluctuation. As such, so long as endometrial support is not lost, amenorrhoea continues • Persistent follicle in metropathia • Feminising dumores of ovary (granulosa cell tumor)

9. IV. Manulanising dumoen of ovary (sertoli leydig cell dumoen) – Androgen excess opposes the effect of estrogen an endometrium V. Lypoesterogenic state Ahlation of ovaries Surgical extirpations VI Induction of multiple ovulation in infertility – leading to premature menopause removal of site of productions of estrogens

10. C. Pituitary and hypothalamic • For normal menstruation do occur, the hypothalamus must be able to secute GnRh, and the pituitary must be able to respond with production and release of FSH and LH dumors may prevent appropriate hormonal section • Ganiophsepgoma • Gumenoma • Tubercular granuloma • Sarroid *** • Der**

11. Pituitary factors: hypopituitarism is rare because a large potion of the gland must be destroyed before hormal secretion affects the patient clinically • Non functioning adenomas • Slohmone security adenomas  Prolactinomas • Cushing disease • Acromegarly • Primary hypothysordesis • Chromophobe adenoma

12. Head injury • Infarction • Infiltrating lesions – lymphocytes hypophipitis • Surgical or radiological ablation • Shuhasis syndrome • Simmonds disease (unulated do pregnancy) • Diabetic vacuities • Such cell • hyperprolactinemia

13. Drugs – tranquilizers, ocp’s, metodopramide, dopamine blacken, antihypertensive, antideprenants, gemetidine, phenothiazines. • Shuhan syndrome : Partial or complete destruction of pit by ischemia caused by venous thrombosis serve pph and shock is associated with postpartum merosis of the pituitary resulting from a hypertensive episode that, in its severe form (pituitary apoplexy) presents with the patient in shock • Hypopituitarisms is associated with hypotension of GH, ACTH, TSH and gonadotropins, therefore, thyroid and adrenal function also must be evaluated.

14. Even PL section is one of the more common causes of amenorrhoea. The menstrual abnormalities are caused by adverse effects of there hormones on GnRh pulse generation and not by direct affects on ovary , Gonodrotropin levels are suppressed.

15. Hypothalamic factors Abnormal secretion of GnRh accounts for 1/3 of patient with amenorrhoea These either hormonal systems that produce excess or insufficient hormones can cause abnormal feedback and adversely affect GnRh secretions prognosis for recovery is better if the precipitating cause of amenorrhoea can be reversed.

16. Causes • GnRh deficiency • Anorexia Newona • 3. Exercise induced: decrease in the frequency of GnRh pulses, which is assessed by measuring a decreased frequency of pulses. • Diffuses in body fat content have been used to explain the different rates of amenorrhoea by spot • 17% of body fat  initiation of menses • 22% of body fat  maintenance of menses

17. The female athlete triad  amenorrhoea osteoposasis and eating disorders 4. Weight loss and dieting Weight loss can cause amenorrhea even if not doesn’t decrease below normal. Loss of 10% body mass in one yr is associated with amenorrhoea Stress Induced : can be causes by abnormalities in neruomodulation in hypothalamic GnRh section, similar to that in occur with exercise and anorexia mucosa. Excess endogenous opoids and  in CRG secretion inhibit the secution of GnRh

18. 5. Pseudocysesis 6. Malnutntia 7. Chronic diseases : DM, renal disorders, pulmonary disorders, liver disease, chronic infections, adhesions disease 8. Obesity : The menstrual disorder is more often irregular uterine bleeding with anorentation rather that amenorrhoea

19. Nututrional Causes • Excessive weight loss in alhtelets and ballet dances • Extreme obesity • 3. Anorexia newosa, bulimia: It is an eating disorder that affects 5% to 10% Criteria for diagnosis can stated in the DSM – IV are refusal do maintain body weight above 15% below normal, an intense for of becoming fat, altered perception of one’s body image and amenorrhea • Amenorrhea may percale, coincide or follow weight loss

20. F. Adrenal factors Adrenal duneosis or hypuplasia Cushing's syndrome Congenital adrenal hyperplasia Adrenogenital syndrome Syprarenal dumors D, E are missing  check

21. G. Thyroid factors • - hypothyroidism – Raised FSH and hyperprolactinemia by direct action on TRH on the galactgshase cells in pituitary • Gracyes disease

22. H. Other causes : Dm, Hb, renal diseases, sene amemia, malnutrition • I. Iatrogenic causes • Post pill amenorrhoea suspension of GnRh release (11%) • Psuchotrophic phenothiazines – Dopamine receptor blocking agents raise the prolacteri level. • Antihypertensive drug like – resespine a dopamine antagonists – dopamine depliting agents raise the PL levels

23. Investigation aims at • To diagnose or confirm the offending factor • To guide the management protocol either to restore menstruation and or fertility • It is not easy to pin point diagnosis only by clinical examination as there is altered cordiated function of HPO arises by some pathology

24. Detailed history • Mode on onset  sudden or gradual preceded by hypomenorrhea or oligo menorrhoea • Sudden change in environment, emotional stress, psychogenic shock or eating disorder • Sudden change in weight – loss or gain • Intake of drys / pills h/o radiotherapy, chemo, surgery

25. Abnormal manifestations • Acne, hirsuites, change in voice • Galactrorrhoea • Headache or visual disturbances • Hot flushes and vaginal dryness • Obstetric history : overzealous curittage, C/s hystrectomy is unware pph or shoch, prolonged lactation • Family history • Medical history

26. INVESTIGATIONS OF SECONDARY AMEMORRHEA Exclude pregnancy Estimation  serum TSH prolactin X ray /CT/MRI – sella durica Normal TSH  PL  abnormalsilla Progesterone challenge chest Hypothepodism Pituitary adenoma Absent Withdrawal bleedy present  HPO axis intact  Adequate endgenous  FSH/LH estimated  LH > 10m 10/ml Or LH >FSH >3  PCOS Loss of progestrone receptor desiased endometrium

27. Bleeding ocurs  Endometrium responsive  E2 – low No bleeding  Non functioning endometrum  Uterine synectrae  HSG or hypteroscopy  So confirm / rule out synechiae Estimative of FSH /LH Low / normal LSC < 5 MIU /ml  GnRh dynamic test High FSH and 40miU/ml  Orarian failure Resistant ovarian syndrome  Age < 30years Hypothalumic (+) Pitutary (-) Kayotope

28. General Exam • Nutritional status • Extreme emaciation or marked obesity • Presence of acne or hirsiutes, • Discharge of milk from breasts

29. Abdominal Ex • Striac • Mass palpable • Pelvic exam • Enlargement of uitaries • Adrenal mass do mass or ovarian dunor

30. 1. Serum FSH and S. prolactin • Sensitive FSH assays can be used do evaluate hypothyroidism and hyperthyroidism • HPL is a common cause of ambulation in women. If elated TSH and PL are found, the hypothyroidism is treated before hyperprolaactinemia. • MRI is done in persistently • 2. Assessment of Estrogen status and prog challenge test, Hot flushes, loss of breast man, depparerenia dryness of vagina are sugg of estrogen lack. • > 50pg/ml  adequate estrogen

31. They respond do PCT A sample vaginal secretions can be obtained and mucosal estrogen response can be demonstrated by presence of superficial cells DEXA do determine bone mineral density in whom hypertrogenism is suspected. This test depends on the presence of estrogen primed endometrium in uterine factor. A positive PCT indicates amenorrhoea secondary to anounlation

32. 3. FSH and LH concentrations A circulating FSH level > 25 to 40 IU/ml indicated on atleast 2 blood samples indicative of hypergonadotropic amenorrhea It patients younger than 30yeras – laccyotype is required do rule out the presence of Y cell time Ovarian biopsy do determine whether follicles are present is not advised. Even if oocytes are found, no method do stimulate those oocytes to acculate.

33. Autoimmune work up for a patient with ovarian facture ANAb’s; RF, ESR (N) APTT  r/o LA S. Electrodytes – Ca2+, (P)  r/o parathyroid ab’s FSH, antithyroid ab’s, antimicosomal ab’s thyroid states 2hth urniary free corteriol – Anti adrenal ab’s (more extensive – parital cell ab’s, Islet of large ab’s anti adrenal abs’s  done yearline / trainst nature

34. In women with FSH and LS < 5MIU/ml thyroid function tests and cortisol can are important other trophic hormones additionally 4. Assessment of pituitary and hypothalamus. If the patient is hypoestrogenic and FSH level is not high, pituitary and hypothalamic lesions shows be excluded.

35. Complete neurological examination • CT or MRI • After anatomic lesions have been excluded, the patients history given importance • Patients with appropriate clinical finding should undergo screening for other hormonal alterations • 1. Androgen levels – hirsute patient • 2. Acromegaly – IGF – I levels • 3. Cushings syndrome – 24 hours urinary cortical levels or 1 mg overweight dexamethosomo suppressions test

36. TREATMENT • The underlying disorders should be treated wherever possible • Patients who are pregnant may be counseled regarding the options for continued care • When thyroid abnormalities are detected, thyroid hormone, radioactive codine or antithyroid drys gives • When hyperpolactinemia is present treatment may include discontinuation of contributing medications medical. Bromocriptive (lepergic acid) dopamine agonist is the DOC dose of 1.25mg orally bed time is started for first week and then gradually increased.

37. Other drugs pregolide (50-150mg) daily minimum side effects cabergoline (0.25mg once or device weekly) there is shrinkage of dumor with therapy. Menstrual cycles restead in 3 months, 90% acculate, 80% conceive • Sergey is considered when there is failure of medical Rx. Transnasla transphenoided excision is done. Radiate therapy is not preferred – 6500chy for 25days. • No abnormality detected. The patient is not anxious about amenorrhea and or fertility. No treatment required. Only assurance is given

38. If anxious about amenorrhea not fertility • OCP’s for 3 cycles  normal endrogen estrogen • Low endogenous estrogen  EE 0.02mg or conjugated equine estrogen 1.25mg daily for 25days MPA 10mg daily for day 16-25. • If patient is anxious for fertility: HAS in primary infertility and dubal factors have to be looked for prior to induction ovulation

39. The treatment of amenorrhea associated with hypthalamic dysfunction also depends on underlying cause : • Hormonally active ovarian dumors are surgically removed • Suy removal, radiation therapy or combinations of both is generally advocated for treatment of CNS dumous other than prolactnoma • Panhypopeteritausm  replacement regimens • These regimens include estrogen replacement for lack of gonadotrpins, corticosteroid replacement for lack of ACTH, thyroid hormone for lack of TSH, decompressing acetate do replace reopening

40. Obesity, malnutritions or chronic diseases, cushing syndrome and accomgaly should be specifically treated. • Pseudocyesis and anxiety and stress induced amenorrhea may respond do assurance and psychotherapy • Exercise induced amenorrhea may improve with moderation of activity, appropriate diet and weight gains • Anorexia newosa needs multidisciplinary approach with sever cases requiring hospitalization. Proper councelling, lot gain advice, behavioural therapy, psychiatric consultation are helpful.

41. Ovarian dumor : Appropriate surgery is done Adrenal disorders When chronic an ovulation is caused by attenuated cogenital adrenal hyperplasia, glucocorticorid administration (dexamethasone 0.5mg at bedtime) is sometimes successful in restoring normal feedback mechanisms thereby permitting regular menstruations and ovulation.

42. Treatment of Cushing’s disease Adrenal dumor  simple adrenalectomy nitotane may be used to produce medical adrenalectomy Enzyme inhibitors like aminoglutithamide or metyrapone has been used to block excess cortisol production Ketocanazole inhibits adrenal steroid biosynthesis Hyperadmogenic state: OCP’s glucocorticoids, antiandrogens

43. Uterine synechia : Adhesions in cervix and uterus can be removed using hystenocopic resection with scissors or electrocautery. A pediatric foley catheter should be placed in uterine cavity 7-10 days post op (+ broadspectria ahteholes) and 2 month cause of high dose estrogen 2.5-5.0mg for 3-6 months with monthly progesterone withdrawal is and do prevent reformation of adhesions

44. Premature Ovarian failure • HRT • Autoimmune disorder – corticosteroids • Fertility potentiality is far and remote. Inductions may be helpful in presence of follicle • Spontaneous recovery and pregnancy have been reported in an occasional care in premature ovarian failure • IVF with donor’s oocyte with total replacement of hormones may be trial • In presence of ‘y’ chromosome, gonadectomy is done to avoid malignancy

45. Hirsutisim • After ruling out androgen – secuting dumor and congenital adrenal hyperplasia, treatment may be aimed at decreasing coaise hair growth • Oral contraceptives :  ovarian androgen • Anti androgens – spironolactone • Flutamids • Cyproterons autate strong progestin and antiandrogen

46. 3. GnRh Against : add back therapy It eliminates ovarian straid production and estrogen progestin add – back therapy allows long term adminstration and protections against osteopaosis 4. 5 reductase inhibitors Finastericle 5. Eflornithine hydrochloride, topical cream for face and chin

47. Pcos: needs individualization of the patient biochemical abnormalities • Hyperandrogenism • Hypersecution of H • High serum estrogens (estrone, estrodial) • Androgenic follicular microenvironment • Low serum FSH • Low serum SHBG

48. Low serum progestrone • Hyperinsclenemia • Hyperprolactinemia • Hyperlipidemia • Weight reductions in obese patients is the first line of treatment. BMI <25 improves menstrual abnormalities hirsuitism, and infertility, it reduces insulin and androgen level.

49. Fertility not Concerned • Androne excess: combined OCP are effective progestin suppress H and estrogen improves SHBG reduces free testosterone level • Newer progestins are best suited • GnRh against : Leuprolide autate 3.75mg 1M or goserelin 3.6mg s/c, every 4 weeks suppress ovarian steroid production • Management of hirrutions • Hyperinsutenemia : is treated do reduce the risks of cardiovascular disease and DM. Endometrium should be protected against the unapproved effects of estrogens.

50. Wanting pregnancy: Ovulation Induction: clomiphene literate with or without dexamethasone or tromocuptive In unresponsive cases pere FSH or HMG along with hCG may be administered backed up with monitoring facilities.