| Fact | Explanation |
|---|---|
| Last regular menstrual period (LMP) and period of amenorrhea (POA) | Primary amenorrhea is absence of menstruation by the age of 16 years in presence of secondary sexual characteristics and by the age of 14 years in the absence of secondary sexual characteristics, thus they will not have an LMP, whereas secondary amenorrhea is absence of menstruation for more than 6 months.[1][2] |
| Cyclical abdominal pain in patients with absent menarche despite normal secondary sexual characteristics. [3] | Imperforate hymen is where the mesodermal membrane that covers the vagina is not perforated as it should be.[3] Transvaginal septum is when the vaginal part of Mullerian duct and the urogenital sinus fail to fuse properly.[5] Both these conditions result in absence of per vaginal menstrual bleeding despite cyclical menstrual pain. [3] |
| History of any uterine surgery, especially of dilatation and curettage/ evacuation of retained products of conception. [11] | This may have lead to intrauterine adhesions, this is knows as the Asherman's syndrome. [11] |
| Abdominal distention, urinary retention, constipation, leg swelling and lower back pain. [4] | In genital outflow tract obstruction (imperforate hymen, complete transverse vaginal septum, vaginal agenesis, cervical dysgenesis) accumulation of menstrual blood in the vagina (haematocolpos) and uterus (hematometra) results in distended abdomen, and compression on urethra, intestine, pelvic vessels and sacral nerve roots causes urine retention, constipation, lower limb edema and back pain respectively. [5] [4] |
| Hirsutism, acne, male pattern alopecia, acanthosis nigricans, obesity [13] | Seen in polycystic ovarian syndrome. Hirsutism(coarse hair in male pattern distribution), acne, male pattern alopecia are due to hyperandrogenism. But virilization do not usually occur, thus suspect androgen secreting tumors if clitoromegaly, voice change, increased musculature occur. [13] |
| Hirsutism, acne, alopecia, early pubarche, high growth velocity leading to tall stature [14] | Associated with non classical congenital adrenal hyperplasia which is an adult onset 21-hydroxylase deficiency due to an autosomal recessive condition. Due to alternative pathway activation there will be elevated levels of more potent androgens such as testosterone. [14] |
| Short stature. [1] | Associated with constitutional delay in puberty and Turner's syndrome. [1] |
| Anorexia nervosa/ Stress/ Strenuous exercise [6] | Leads to reduced GnRH secretion from hypothalamus, thus reduced FSH/LH secretion leading to amenorrhoea. (hypogonadotropic hypogonadism) [1] |
| Anosmia | Associated with Kallman syndrome, due to KAL 1 gene mutation there is a defect in GnRH neuron migration, leading to reduced GnRH secretion. [7] |
| Features of hypothyroidism: lethargy, cold intolerenuce, weight gain, constipation | Both primary and secondary hypothyroidism are associated with amenorrhea. In primary hypothyroidism there is elevated levels of TRH, due to defective negative feedback. TRH increases prolactin secretion leading to amenorrhoea, other features of hyperprolactinaemia will also be present in these patients. [8][9] Secondary hypothyroidism is associated with pituitary adenoma secreting prolactin leading to hyperprolactinaemia. [9] Both primary and secondary hypothyroidism maybe associated with suprasellar enlargement of pituitary gland. [9] |
| Galactorrhoea | Due to pituitary adenoma secreting prolactin. Prolactin suppresses LH and FSH secretion leading to amenorrhoea. [10] |
| Features of Cushing's syndrome: central obesity, striae, buffalo hump, easy bruisibility, hypertension, proximal muscle weakness[1] | Due to pituitary adenoma with both excess ACTH and prolactin. [15] |
| Visual disturbances, headache [1] | Associated with pituitary tumor, since is compresses on optic chiasma, it can cause bitemporal hemianopia. |
| Breast feeding/ breast stimulation | Causes elevated levels of prolactin. [1] |
| Features of liver/ renal failure. | Liver failure or renal failure results in elevated levels of prolactin due to defective metabolism. [1] |
| Family history of delayed puberty. [1] | Constitutional delay of puberty represents 6% of primary amenorrhoea. These patients will have short stature and poor development of secondary sexual characteristics. [1] |
| Family history of polycystic ovarian syndrome and metabolic diseases are present in polycystic ovarian syndrome(PCOS).[12] | Familial clustering is noticed in PCOS [12] |
| Drug/ illicit substances history | Antipsychotics, antidepressants, antihypertensives, histamine H2 receptor blockers, opiates, cocaine are known to cause hyperprolactinaemia. [1] |
| History of chemotherapy, pelvic radiation, mumps, other autoimmune conditions [1] | Associated with premature ovarian failure. [1] |
| Fact | Explanation |
|---|---|
| Secondary sexual characteristics: Pubarche and thelarche | In the absence of these primary amenorrhea can be diagnosed at the age of 14 years. Important in evaluation of primary amenorrhoea. Absence suggest hypogondism which maybe hypergonadotrophic(premature ovarian failure, Turner's syndrome) or hypogonadotrophic(Constitutional)[4] |
| Short stature.[4] | Associated with constitutional delay in puberty and Turner's syndrome. [1] |
| Features of Turner's syndrome: short stature, neck webbing, widely spaced nipples, wide carrying angle (cubitus valgus) [5] | They will also have underdeveloped secondary sexual characteristics. [5] |
| Features of hyperandrogenism: Hirsutism, acne, increased musculature | Seen in both PCOS and adult onset adrenal hyperplasia. [6][7] |
| Abdominal palpation: Mobile, non tender mass arising from the pelvis [1] | In genital outflow tract obstruction (imperforate hymen, complete transverse vaginal septum, vaginal agenesis, cervical dysgenesis) accumulated blood can be palpated abdominally. [1][2] |
| Genital examination will reveal bulging bluish hymen which further bulges on Valsalva manouevre. [1] | Haematocolpos is seen as bluish bulge on inspection of the vagina and unlike complete transverse vaginal septum, imperforate hymen demonstrates bulging on Valsalva manouevre.[1] |
| A blind vaginal pouch seen in vaginal examination. [2] | Seen in genital outflow tract obstruction (complete transverse vaginal septum, vaginal agenesis, cervical dysgenesis) [3] |
| Visual field-Bitemporal hemianopia | Associated with pituitary tumor. [4] |
| Fact | Explanation |
|---|---|
| Hypogonadotropic hypogonadism[1] | Due to hypothalamus disturbances: stress, severe exercise, Sheehan syndrome, constitutional delay, chronic illness, Kallmann syndrome, malnutrtion. [1][5] |
| Hypergonadotropic hypogonadism[1] | Maybe due to gonadal dysgenesis(Turner's syndrome), PCOS or premature ovarian failure [1] |
| Normogonadotropic-congenital[1] | Primary amenorrhea: Androgen insensitivity syndrome, Müllerian agenesis [1] |
| Normogonadotropic with hyperandrogenism[1] | PCOS, androgen secreting tumor, exogenous androgens[1][4] |
| Normogonadotropic with outflow tract obstruction[1] | Primary amenorrhea: Imperforate hymen, transverse vaginal septum Secondary amenorrhea: Asherman syndrome, cervical stenosis [1][3] |
| Hypothyroidism | Due to reduced negative feedback on TRH leading to excess prolactin secretion. [2] |
| Fact | Explanation |
|---|---|
| Ultra sound scan of the abdomen shows a homogenous, hypoechoic mass in the uterus and vagina. [1] | Imperforate hymen-collection of menstrual blood is seen in ultrasound scan. |
| Elevated FSH, LH levels. [2] | Indicates hypergonadotropic hypogonadism. [2] |
| Low FSH and LH levels. [2] | Indicates hypogonadotropic hypogonadism.Most common cause is constitutional delay. [2] |
| LH/FSH ratio ≥2 [6] | Suggestive of PCOS. [6] |
| Prolactin levels [2] | Hyperprolactinaemia is associated with amenorrhoea and many underlying causes may result in this condition. If very high prolactin levels are detected (> 100 ng per mL), its usually due to pituitary adenoma or empty sella syndrome. [2] |
| 17-hydroxyprogesterone level | <200 ng/dL (<6 nmol/L) in the follicular phase excludes 21-hydroxylase deficiency and ACTH stimulation with a 30 minute value of ≥1,000 ng/dL is diagnostic. [6] |
| Skull X ray | Enlarged sella turcica can be seen in pituitary tumor. |
| Standard karyotyping: 45 X pattern or XY pattern | In a patient with features of Turner's syndrome or short stature, a pattern of 45 X or combination of 45 X and 45 XX (mosaic pattern) indicates Turner's syndrome. Other sex chromosome abnormalities including presence of abnormal Y chromosome maybe seen in Turner's syndrome. [4] Presence of XY karyotype in primary amenorrhoea with secondary sexual characteristics indicate androgen insensitivity syndrome.[5] |
| Ultrasound scan of abdomen to confirm the presence of uterus is done when Müllerian agenesis is suspected. [2] | Müllerian agenesis is suspected when secondary sexual characteristics are present despite amenorrhea and accounts for 15% of primary amenorrhea. This occur due to abnormal activation of Müllerian inhibitory substance which results in malformation of female genital tracts. [2] |
| Ultrasound scan showing increased ovarian volume (>11 mm) with ≥12 follicles of 2-9 mm in diameter [6] | Suggestive of PCOS [6] |
| Hysteroscopy/ Hysterosalpingography. [3] | Intra uterine adhesions, polyp, cyst that are blocking the outflow can be seen. [3][2] Hysteroscopy is the gold standard method to diagnose Asherman syndrome. [3] |
| MRI of sella turcica. | Reveals enlarged sella turcica in pituitary tumor, both micro and macroadenoma can be detected. [2] |
| Fact | Explanation |
|---|---|
| If a microadenoma has been detected in MRI, patient should be followed up with serial prolactin levels and imaging. [1] | Because microadenomas are slow growing and rarely malignant, thus while patient is on treatment with dopamine agonists for symptom, she should be followed up for any changes. [1] |
| Fact | Explanation |
|---|---|
| Hymenectomy with a cruciate incision for imperforate hymen. [1] | At hymenectomy the accumulated menstrual blood will be evacuated and the incision will allow per vaginal discharge of menstrual blood. |
| Non surgical and surgical procedures for neo-vaginal formation is available in outflow tract obstruction due to Müllerian agenesis. [2][3] | Manual dilatation of the vagina through the identified vaginal dimple is successful in self-motivated woman but takes several months of dilatation. In those who have failed non surgical methods and those who wish surgical neo vaginal formation can be done. [3] |
| Thyroxin for primary hypothyroidism and secondary hypothyroidism neurosurgery is considered after exclusion of primary hypothyroidism. [4] | Both primary and secondary hypothyroidism is associated with hyperprolactinaemia, galactorrhoea and suprasellar enlargement of pituitary gland. Thus, first thyroid levels should be corrected to exclude primary hypothyroidism and then neurosurgery should be considered if secondary hypothyroidism is confirmed.[4] |
| Dopamine agonist (cabergoline superior than bromocriptine in effectivity and tolerability) for treatment of hyperprolactinaemia.[5] | In hyperprolactinamia, underlying cause should be sort for and treated. In cases of microadenoma which are usually benign and slow growing dopamine agonist can be given while patient is monitored with serial prolactin levels and imaging. In microadenoma dopamine agonist can be given, but neurosurgery is also considered. [5] |
| Transsphenoidal resection of microadenoma.[5] | For resection of pituitary microadenomas, in some cases craniotomy maybe necessary. |
| Multi disciplinary team including general practitioner approach is used in management of Turner's syndrome. [6] | Osteoporosis, cardiovascular complications, infertility should be addressed.[6] Follow up with 2D echocardiogram for possible aortic root dilatation should be done.[6] Cryopreservation of oocytes or ovarian tissue is possible in some patients with Turner's syndrome while others can become pregnant with usage of donor oocytes. Patient should be counseled regarding possible outcomes, increased risk of hypertension and increased mortality due to aortic dissection before pregnancy is assisted. [7] |
| Multidisciplinary team should be involved in management of androgen insensitivity syndrome. Sex-hormone replacement therapy should be started at puberty and should be continued afterwards. Gonadectomy should be done. [8] | These patients are prone to develop gonadal tumours later in life, thus gonadectomy prevents this.[8] |
| Oral contraceptives and ovulation induction in PCOS.[9] | Oral contraceptives are used to normalize the menstrual cycle in PCOS and ovulation induction is used to achieve fertility. [9] Combined oral contraceptives also used in combination with spiranolactone which is also an antihypertensive agent, to reduce hirsutism. Metformin and weight reduction helps insulin insensitivity. Cardiovascular risk factors should also be addressed in long term treatment of PCOS. [9] |
| Ovulation induction and symptomatic treatment for patients with 21 hydroxylase deficiency.[10] | Prednisolone and dexamethasone are used in daily treatment. Patients on glucocorticoid should be advised regarding stress doses. Those who want to achieve fertility may benefit from clomiphene ovulation induction. [10] |