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MENSTURAL CYCLE DISORDERS (Classification According to Hypothalamic…
MENSTURAL CYCLE DISORDERS
ABNORMAL UTERINE BLEEDING (AUB)
Classification of causes
PALM – COEIN
Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia
Coagulopaties, Ovulatory disorder, Endometrial, Iatrogenic, Not yet classified
Classification requires access to transvaginal ultrasound and hysteroscopy.
POLYPS
Generally benign but a small minority may have atypical or malignant features
SYMPTOMS: usually intermenstrual bleeding
DIAGNOSIS: USG (contrast sonography) and diagnostic hysteroscopy
TREATMENT: ablation
ADENOMYOSIS
Existence of endometrial glands stroma within the myometrium
SYMPTOMS: combination of AUB (generally heavy menstrual bleeding), dysmenorrheal and other pelvic pain (frequently found in women undergoing hysterectomy who have no symptoms before surgery)
DIAGNOSIS:
Magnetic resonance imaging (most sensitive)
USG: a globular uterine configuration; poorly defined endometrial-
myometrial junction; myometrial echogenic linear striations; thickening of the myometrium; asymmetry of the anterior-posterior myometrial thickness; irregular myometrial cystic spaces; and a heterogeneous myometrial echotexture
Pathology: Endometrium is demonstrated at least 2.5 mm (or 4mm) beneath the endomyometrial junction
TREATMENT: For further details see corresponding seminar
LEIOMYOMA
Cause of AUB in leiomyomas: increased endometrial surface area and the presence of a fragile and engorges plexsus of perimyoma vasculature.
COAGULOPATIES
The most common of these is von Willebrand disease - approximately 13% of women with heavy menstrual bleeding)
ENDOMETRIAL
At the present time, there are no clinically available specific tests for these disorders, so the diagnosis of AUB-E is probable if there are no other identifiable abnormalities
NOT YET CLASSIFIED
Unschedulde uterine bleeding arising from the endometrium can occur during the use of continuously administered local or systemic gonadal steroid therapy (eg estrogens, progestogens), GnRH agonists, aromatase inhibitors, selective estrogen receptor modulators or “SER<’s, progesterone receptor modulators or “PRMs”).
OVULATORY DISORDERS
Normal menstruation = eumenorrhea
Regular, cyclic uterine bleeding, of normal duration and intensity
– Cycle length: 25 - 35 days
– Menstruation length: 3 - 5 days
– Physiological blood loss : 30 - 70 ml
PRIMARY AMENORRHOEA
LACK OF MENSTRUATION IN GIRLS:
at the age of 15 years in girls with normal secondary sex characteristics
five years after the development of breasts (if breast development began before 10 y/a)
at the age of 13 years with absence of sex development characteristics (breast development)
SECONDARY AMENORRHOEA
Lack of menstrual bleeding for at least 3 months in women with regular menstruation.
Lack of menstrual bleeding for at least 6 months in women with irregular menstruation.
Physiologic states of amenorrhoea: pregnancy, lactation
TYPES OF MENSTRUATION DISORDERS
Polymenorrhoea < 22-24 days
Oligomenorrhoea >35 days (fewer than six to eight periods per year)
Hypomenorrhoea: 1-2 days of bleeding, blood loss < 50 ml
Hypermenorrhoea: blood loss > 100 ml, menstruation occurring in the correct time and time.
Metrorrhagia - irregular menstruation that occurs between the expected menstrual periods
Dysmenorrhea - involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain
PREMENSTRUAL SYNDROME (PMS)
Set of physical, emotional, and behavioral symptoms that occur during the last week of the luteal phase (a week before menstruation) in most cycles.
The symptoms typically do not start until at least day 13 in the cycle, and resolve within 4 days after bleeding begins.
Women may begin to have premenstrual syndrome symptoms at any time during their reproductive years, but it usually occurs when they are in their late 20s to early 40s.
The symptoms remain constant until menopause, variable from cycle to cycle.
WHO CLASSIFICATION OF THE MENSTRUAL DISORDERS
I. Hypothalamic & pituitary insufficiency
II. Hypothalamic & pituitary disorders
III. Primary ovarian insufficiency
IV. Congenital or acquired disorders of the uterus
V. Tumors of hypothalamic-pituitary region producing prolactin (PRL)
VI. Disorders of hypothalamic-pituitary function connected with hyperprolactinaemia
VII. Inflammation, posttraumatic causes or tumors of hypothalamic-pituitary region
Classification According to Hypothalamic-Pituiary-Ovarian Function, Pelvic Anatomy And Presence Of Secondary Sexual Characteristics
Hypergonadotropic Hypogonadism
PRIMARY (absence of secondary sexual characteristics and primary amenorrhea)
MOST patients have primary amenorrhea and lack secondary sexual characteristics - occasionally patients with a partial deletion of the X chromosome, mosaicism, or pure gonadal dysgenesis (46,XX) may synthesize enough estrogen in early puberty to induce breast development and a few episodes of uterine bleeding (secondary amenorrhea, occasionally ovulation and pregnancy are possible)
GENETIC DISORDERS
TURNER SYNDROME (45,X)
Patients with Turner syndrome initially have normal ovarian development in utero.
Amenorrhea is the result of accelerated atresia of the follicles at young age (before puberty)
45, X0 – PRIMARY AMENORRHEA
45, X0 / 46,XX – SECONDARY AMENORRHEA (PREGNANCY IS POSSIBLE, SECONDARY OVARIAN FAILURE)
PURE GONADAL DYSGENESIS = SWYER SYNDROME (46,XY)
Phenotypically female with sexual infantilism, primary amenorrhea, normal stature, and no karyotypic abnormalities (46,XX or 46,XY).
Patients with PGD have localized genetic alterations.
The gonads are usually atrophic ("streak gonads")
most frequently (~20%) mutations in the SRY (sex- determining region gene on the Y chromosome).
Mutations of the SRY cause that the testes never form and anti- müllerian hormone/testosterone/DHT is not produced (female phenotype: vagina, uterus, and fallopian tubes, female sex identification) Germ cells in the gonads are lost before birth.
No spontaneous breast development, scarce pubic/axillary hair, tall stature, primary amenorrhea (first symptoms).
The streak gonads must be surgically removed because of the increased risk for developing germ cell tumor.
Treatment – induction of sexual maturation using estrogens then hormonal replacement therapy.Pregnancy possible – oocyte donor only
RARE ENZYME DEFICIENCIES
Congenital Adrenal Hyperplasia 17a-Hydroxylase Deficiency, Aromatase Deficiency, Galactosemia
damage to the ovaries before the onset of puberty
can lead ovarian insufficiency.
Irradiation of the ovaries, chemotherapy with alkylating agents.
DIAGNOSIS OF PRIMARY HYPERGONADOTROPIC HYPOGONADISM:
ANAMNESIS,PHYSICAL / GYNECOLOGICAL EXAMINATION / USG,FSH, ESTRADIOL,KARTIOTYPE / MUTATION ANALYSIS
SECONDARY (PRESENCE OF SECONDARY SEXUAL CHARACTERISTICS AND SECONDARY AMENORRHEA)
PRIMARY OVARIAN INSUFFUCIENCY (POI)
presence of amenorrhea for 4 months or more.
Must be confirmed by two serum FSH levels (>25IU/ml) in the menopausal range for a woman who is less than 40 years of age.
Some women with POI retain intermittent ovarian function for many years (pregnancy may occur)
Symptoms: hot flashes, vaginal dryness, tachycardia, sleeping disorders, low libido, night sweats
POI ASSOCIATED WITH AUTOIMMUNITY
autoimmune oophoritis is a relatively rare condition, (less than 5% of women who present with spontaneous POI)
DIAGNOSIS
Two FSH levels in the menopausal range (>30-40 μIU/mL), measured at least 1 month apart; estradiol <20 pg/ml; atrophic ovaries on TV USG, low AMH
A karyotype should be performed as a part of the routine evaluation after the diagnosis of POI/POF is established
TREATMENT
Cyclical therapy with estrogens and progestins (to eliminate the symptoms of estrogen deficiency and to maintain bone density)
Progestins should be administered cyclically, 10-14 days each month, to prevent endometrial hyperplasia that unopposed estrogen may cause.
RADIATION OR CHEMOTHERAPY
Radiation dose of 800 cGy causes sterility in most patients. Ovarian failure can be caused by as little as 150 cGy in some patients, especially if they are older than 40 years of age
Chemotherapy: mainly alkylating agents - cyclophosphamide
HYPOGONADOTROPIC HYPOGONADISM
PRIMARY (ABSENCE OF SECONDARY SEX CHARACTERISTICS AND PRIMARY AMENORRHEA) (WHO GROUP 1)
DISORDERS OF HYPOTHALAMUS / PITUIARY BEFORE ONSET OF PUBERTY (TUMORS, SURGERY, RTX, INFLAMATION, PRIMARY HIPOPITUIARISM), FSH / LH DEFICIENCY
Hypothalamus fails to secrete GnRH or pituitary disorder associated with inadequate production or release of gonadotropins (LH / FSH).
PHYSIOLOGIC DELAY – MOST FREQUENT:
delay of puberty is the most common manifestation of primary hypogonadotropic hypogonadism.
Primary amenorrhea result from delayed activation of the GnRH pulse generator.
Physiologic delay is a diagnosis if exclusion that is difficult to distinguish from insufficient GnRH secretion.
KALLMANN SYNDROME:
Hypogonadotropic hypogonadism with associated anosmia/hyposmia and pubertal delay and a normal response to exogenous gonadotropins.
Result of deficient hypothalamic secretion of GnRH.
Clinically: primary amenorrhea, no secondary sex characteristics, low FSH/LH, low estradiol, female karyotype
SECONDARY (PRESENCE OF SECONDARY SEX CHARACTERISTICS AND SECONDARY AMENORRHEA) (WHO GROUP 1)
ORGANIC DISORDERS OF HYPOTHALAMUS / PITUIARY
LESIONS OF THE HYPOTHALAMUS OR PITUITARY
Most frequently: craniopharyngiomas, germinomas, sarcoid granulomas
Tumor destroys hypothalamus/pituary or causes compression of the pituary stalk (no stimulation of pituary gland, lack of FSH/LH, additionally hyperprolactinemia due to block dopamine release)
The surgical and radiologic treatment of tumors may in itself cause further abnormalities in hormone secretion.
SHEEHAN SYNDROME:
caused by postpartum necrosis of the pituitary resulting from a severe hypotensive episode (hemorrhage during/after delivery)
Patients with a mild form of postpartum pituitary necrosis cannot lactate, lose pubic and axillary hair, and do not menstruate after delivery.
In severe cases acute symptoms develop due to abrupt cessation of all pituiary hormones production / release
EMPTY SELLA SYNDROME:
Sella turcica is not entirely filled with pituitary tissue, pituitary gland is compressed by a defect in the diaphragm sella (filled with cerebrospinal fluid)
FUNCTIONAL
STRESS
Similar to those that occur with exercise and anorexia nervosa. Excess endogenous opioids and elevations in CRH secretion inhibit the secretion of GnRH
EXTREME EXERCISE
5-25% of sportswomen, Increased cortisol, catecholamines
Disturbed correct pulsatile GnRH secretion
Woman athlete triad:
Eating disorders (low energy diet)
Oligomenorrhea / amenorrhea
Osteoporosis / osteopenia
These patients are usually hypoestrogenic, but less severe alterations may cause minimal menstrual dysfunction (anovulation or luteal phase defect). Approximately a minimum of 17% body fat is required for the initiation of menses and 22% body fat for the maintenance of menses.
EATING DISORDERS
Amenorrhea occurs in severe decrease in GnRH pulsatility. With less severe alterations in GnRH pulsatility, anovulation and oligomenorrhea can occur.
ANOREXIA NERVOSA
Disturbs correct pulsatile GnRH secretion (and in consequence LH and sometimes FSH), LH/FSH ratio as in prepubertal age
Hypercortisolism is present despite normal ACTH levels.
Binge eating can cause amenorrhea even if weight does not decrease below normal. Loss of 10% body mass in 1 year is associated with amenorrhea.
GnRH test: too low increase of LH (<3-4 times), normal FSH response (2-3 times)
Osteoporosis / osteopenia
PRL might be decreased
Only 50% of cases can be successfully treated
Treatment: normal alimentation, hormonal replacement therapy (oral contraceptives contain too high dose of estrogen), psychotherapy
DIAGNOSTICS
Primary HYPO-HYPO
Anamnesis/examination: primary amenorrhea, no secondary sex characteristics
FSH<1; LH<0,5, E2<20pg/ml
Progesterone challenge test: negative (no bleeding)
Progesterone-estrogene challenge test: positive (presence of bleeding)
Secondary HYPO-HYPO
Anamnesis/ examination: secondary amenorrhea, secondary sex characteristics present
FSH<4; LH<3, E2<20pg/ml
Progesterone challenge test: negative (no bleeding)
Progesterone-estrogene challenge test: positive (presence of bleeding)
GnRH test - stimulation of pituary gland. If there is primary pituary insufficiency there is no LH / FSH increase
TREATMENT
HORMONAL REPLACEMENT THERAPY
Cyclic estrogen and progestogen therapy to initiate, mature, and maintain secondary sexual characteristic. (in secondary amenorrhea – only to maintain)
1.If the patient is short in stature, higher doses of estradiol should not be used because premature closure of the epiphyses should be avoided.
2.Estrogen must be given daily in combination with progestogen to prevent hyperplasia that could result from unopposed estrogen stimulation of the endometrium in patients with a uterus (risk of endometrial cancer)
TARGETED THERAPY (IF POSSIBLE)
CNS tumors – surgery
Prolactinomas and hyperprolactinemia respond to dopamine agonists (bromocriptine or cabergoline).
Malnutrition, anorexia nervosa, neoplasia, and chronic diseases – adequate treatment
Physiologic delay of puberty, the only management required is reassurance that the anticipated development should occur
INFERTILITY TREATMENT
Ovulation induction with gonadotropins is generally successful. In patients without ovarian function - oocyte donation
general diagnostic considerations
PREGNANCY TEST (serum or urinary human chorionic gonadotropin)
BASIC TESTS: LH/FSH, ESTRADIOL, 17OH-PROGESTERONE, TSH, PROLACTIN, ANDROGENS (TESTOSTERONE, ANDROSTENDION, dhea-s)
Progesterone Withdrawal Test - performed to demonstrate estrogen effect on the endometrium.
Progesterone induce a withdrawal bleeding if the circulating serum estradiol level is at least 50 pg/mL.
Progesterone-Estrogen Withdrawal Test - performed to demonstrate presence of endometrium (uterus) or normal outflow of the blood during menstruation (in absence of endogenous estradiol)
Gn-RH test – performed to determine pituary gland function (and hypothalamus function indirectly).
Classification According to Hypothalamic-Pituiary-Ovarian Function, Pelvic Anatomy And Presence Of Secondary Sexual Characteristics
AMENORRHEA WITH ABNORMALITIES OF PELVIC ANATOMY (WHO group VI)
Amenorrhea occurs if there is blockage of the outflow tract, or if there is no functioning uterus.
: Asherman syndrome, cervical stenosis
PRIMARY AMENORRHEA
congenital disorders
Congenital malformations of the mullerian ducts
Imperforate hymen
Transverse vaginal septum
Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome (congenital aplasia of the uterus and upper two thirds of the vagina)
Because the ovaries function normally and produce estradiol, breasts develop normally. Pubarche is also normal - pubic hair remains normal.
androgen insensitivity syndrome (46 XY)
Phenotypic females with complete congenital androgen insensitivity develop secondary sexual characteristics but do not heave menses.
Defect that prevents normal androgen receptor function, leading to the development of the female phenotype.
CLINICAL FEATURES
high stature, developed breasts, no pubic hair, inguinal hernias, no uterus, short or absent vagina
The phenotypic appearance in patients with this condition is female, but hormonal pattern is male.
Serum testosterone is in the normal male range.
Because antimullerian hormone is present and functions normally in these patients, internal female structures such as a uterus, vagina, and fallopian tubes are absent.
Testes are present in the abdomen or in inguinal hernias because of the presence of normally functioning genes on the Y chromosome.
Patients experience abundant breast development at puberty.
Testosterone is not present during development to suppress the formation of breast tissues and after puberty the conversion of testosterone to estrogen stimulates breast growth.
SECONDARY AMONORRHEA
Asherman syndrome (adhesion and/or fibrosis of endometrium , most often associated with dilation and curettage)
Cervical stenosis resulting from surgical removal of dysplasia.
DIAGNOSTICS
Most congenital abnormalities can be diagnosed by physical examination
USG / MRI / VAGINOSCOPY / VAGINOGRAPHY
Asherman syndrome: hysterosalpingography
Historically: progestogen challenge followed by estrogen / progestogen challenge (BOTH NEGATIVE)
TREATMENT
In patients with complete androgen insensitivity, the testes should be removed after pubertal development is complete to prevent malignant degeneration. Estrogen therapy if desired (no need for progesterone – no uterus)
Adhesions in the cervix and uterus can be removed using hysteroscopic resection with scissors or electrocautery.
AMENORRHEA IN THE PRESENCE OF NORMAL PELVIC ANATOMY AND NORMAL SECONDARY SEXUAL CHARACTERISTICS
CONGENIAL ADRENAL HYPERPLASIA "LATE-ONSET"
Serum 17-OH progesterone, >1000 ng/dl confirms the diagnosis., >200ng/dl - synthetic corticotropin (Synacthen) stimulation test is necessary (>1000 ng/dl)
Testosterone levels in these women may be mildly elevated, or simply above average
TREATMENT OF NCAH: Low dose dexamethasone – in symptomatic cases
Pregnancy must be considered in all women with amenorrhea
POLICYSTIC OVARIAN SYNDROME (PCOS) (WHO GROUP 2)
One of the most common endocrine disorders of reproductive-age women (4-12%)
MECHANISM FOR ANOVULATION AND ELEVATED ANDROGEN LEVELS:
under the increased stimulatory effect of luteinizing hormone (LH) stimulation of the ovarian theca cells is increased. These cells, in turn, increase the production of androgens. Due to increased number of small follicles the estradiol concentration is quite high (constantly) which also blocks necessary FSH fluctuations – no stimulation of growing follicle
CLINICAL PRESENTATION
Oligomenorrhea / amenorrhea
Hirsutism (male hair distribution pattern: upper lip, on the chin, around the nipples, and along the linea alba of the lower abdomen)
Male-pattern hair loss (androgenic alopecia)
Acne
High serum concentrations of androgenic hormones - testosterone, androstenedione, and dehydroepiandrosterone sulfate
Peripheral insulin resistance and hyperinsulinemia (10% of women with PCOS have type 2 diabetes mellitus, and 30-40% of women with PCOS have impaired glucose tolerance by 40 years of age)
Frequently obesity
Polycystic ovaries are enlarged bilaterally and have a smooth, thickened capsule with many small follicles places peripherally
Elevated LH and FSH (LH/FSH >1)
HYPERTHECOSIS - extreme form of PCOS (clitoromegaly, increased muscle mass, voice deepening)
ACANTHOSIS NIGRICANS - diffuse, velvety thickening and hyperpigmentation of the skin. It may be present at the nape of the neck, axillae, area beneath the breasts, intertriginous areas, and exposed areas (eg, elbows, knuckles). In patients with PCOS, acanthosis nigricans is thought to be the result of insulin resistance.
DIAGNOSIS
requires the exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism (adrenal or ovarian tumors, thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinemia, acromegaly, and Cushing syndrome)
European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) recommended that at least 2 of the following 3 features are required for PCOS to be diagnosed:
-Oligo-ovulation or anovulation manifested as oligomenorrhea or amenorrhea
-Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
-Polycystic ovaries (as defined on ultrasonography 10cm3 or at least 12 follicles)
HIRSUTISM EVALUATION
The modified Ferriman-Gallwey (mFG) score grades 9 body areas from 0 (no hair) to 4 (intense), including the upper lip, chin, chest, upper abdomen, lower abdomen, thighs, back, arm, and buttocks. A total
score of 8 or more is considered abnormal for an adult white woman; a score of 36 is the most severe.
PCOS in adolescents:
Oligomenorrhea >45 days or amoenorrhea > 3 months BUT at least 2 years after menarche
Hiperandorgenism marker: hirsutism (not acne)
Ovarian volume >10cm3 is not an indicator of PCOS
LABORATORY TESTS
free testosterone level (or FAI – free androgen index total testosterone / SHBG)
dehydroepiandrosterone sulfate (DHEA-S), may be normal or slightly above the normal range (mainly produced by adrenal glands)
androstenedione (usually increased – 60% in ovaries / 40% in adrenal glands)
FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated (LH/FSH ratio >3) – CURRENTLY NOT INCLUDED TO PCOS CRITERIA
TREATMENT
LIFESTYLE CHANGES: diet and exercise
3 goals of treatment
Protection of endometrium
The chronic anovulation in PCOS leads to constant endometrial stimulation with estrogen without progesterone, and this increases the risk of endometrial hyperplasia and carcinoma. Induction of withdrawal bleeding with progestogens a minimum of every 3-4 months
Hirsutism / acne
Cosmetics methods (more effective than pharmacologic treatment of hirsutism/acne)
Oral Contraceptives (decreasing ovarian androgen production and increasing circulating levels of sex hormone-binding globulin).
Antiandrogens
Spironolactone
Flutamide (rare complication of hepatotoxicity)
Cyproterone acetate (usually administered in combination with wthinyl estradiol on an oral contraceptive).
Finasteride (5α-reductase inhibitor)
All antiandrogens are teratogenic as they may lead to feminization of the external genitalia of a male fetus (ambiguous genitalia). Therefore, antiandrogens are typically used in combination with oral contraceptives.
Infertility
clomiphene is first-line treatment. Second-line therapy: exogenous gonadotropins or laparoscopic ovarian surgery (electrocauterisation)
HYPERPROLACTINEMIA
5-14% of patients with secondary amenorrhea
Prolactin-secreting adenomas are divided into 2 groups:
microadenomas - smaller than 10 mm
macroadenomas - 10 mm or larger.
Typically: oligomenorrhea/amenorrhea (hiperPRL – abnormal GnRH secretion), galactorrhea, infertility.
Normal fasting values 5-30 ng/mL. Prolactinoma is likely if greater than 250 ng/mL
Intensity of symptoms
30-50 ng/mL – short luteal phase, decreased libido
50-75 ng/mL – oligomenorrhea/amonorrhea (80%), galactorrhea (50%), decreased libido
more than 100 ng/mL – hypogonadism (85%), oligomenorrhea/amonorrhea (90%), galactorrhea (66%), decreased libido
Causes (excluding pregnancy / breast feeding)
increased activity of pituitary lactotrophs
nonfasting sample, excessive exercise, sexual activity, a history of chest wall surgery or trauma, renal failure, cirrhosis.
pharmacologic (metoclopramide, antipsychotic drugs, verapamil, estrogens, antiandrogens, H2-blockers [cimetidine])
hypothalamic-pituitary dopaminergic pathways disruption – surgery,RTX-therapy, injury, tumors (dopamine from hypothalamus constantly blocks PRL secretion)
primary hypothyroidism (increased TRH)
MACROPROLACTINEMIA (15-26%) - apparent increase in serum prolactin without typical symptoms.
Diagnostics
25% polyethylene glycol is added to the serum (precipitation of PRL di- and polymers). Macroprolactinemia is diagnosed if PRL after the polyethylene glycol is <40%.
TREATMENT OF HYPERPROLACTINEMIA:
Withdrawal of drugs that cause hyperprolactinemia (IF POSSIBLE)
Treatment of hypothyroidism
Patients with hyperprolactinemia and no symptoms can be monitored without treatment.
Dopamine agonists
Bromocriptine - lowers the prolactin level in 70-100% of patients.
Cabergoline - more effective and causes fewer adverse effects than bromocriptine
Quinagolide
EVALUATION
A PREGNANCY TEST (URINE OR SERUM hCG):
Clinical/laboratory assessment of estrogen status, TSH, PRL, FSH, transaginal ultrasound, Imaging of the pituitary and hypothalamic, Adequate tests if any systemic disease is suspected
ASSESSMENT OF ESTROGEN STATUS
Clinically: vaginal dryness or hot flashes indicate low estradiol
Serum estradiol level higher than 40 pg/ml is indicative of significant estrogen production
Vaginal ultrasound demonstrating a thin endometrium suggests that a patient is hypoestrogenic.
PELVIC ULTRASONOGRAPHY: congenital abnormalities of the uterus, cervix, and vagina, or absence of these organs, PCOS features (12 follicles / 10cm3 volume)
MAGNETIC RESONANCE IMAGING can detect hypothalamic/pituitary lesions.
HYSTEROSALPINGOGRAPHY AND HYSTEROSCOPY - Asherman syndrome.