Principles of Gynecological Endocrinology
Menarche - 1st menstruation
Menopause – last menstruation
Amenorrhea - absence of menstruation
Oligomenorrhea – rare menses (40 d – 6 months)
Hypomenorrhea – reduction in duration and/or amount of menstrual bleeding
Polimenorrhea – frequent menses (less than 25 d)
Hypermenorrhea - long and/or extensive menstrual bleeding
Dysfunctional uterine bleeding – irregularity without organic pathology
Reproductive cycle
1 5 14 28
FSH
E2
21P
LH
GnRH
ovulation
No implantation
Amenorrhea
Primary – woman has menstruated never before
Secondary – 6 months interval after last menstruation
Amenorrhea - Causes
Pregnancy
Hypothalamic-Pituitary Dysfunction
Ovarian dysfunction
Pathology of the genital outflow tract
Hypothalamic-Pituitary Dysfunction
Disturbances of the pulsatile manner of the GnRH release or FSH and LH releaseCauses Congenital – Isolated hypogonadotropic hypogonadism Functional
Weight loss Excessive exercise Obesity
Drugs Psychogenic causes
Anorexia nervosa Chronic anxiety
Head injury Neoplastic diseases of the hypothalamo–pituitary region
Diagnosis – medical history; low E2, PRL, low FSH and LH levels; CT; NMR; GnRH test
Premature Ovarian failure
Lack of ovarian folliclesResistance to pituitary stimulation (FSH, LH)Additional symptoms similar to those associated with menopauseHot flushes, mood changes, sleep
disturbances, headaches, vaginal dryness and/or pruritus, dyspareunia, diaphoresis, altered libido
Ovarian failureCauses Chromosomal abnormalities
45,X gonadal dysgenesis (Turner,s syndrome) 46,XY (Sweyer,s syndrome) Androgen insensitivity syndrome
Gonadropin-resistant ovary syndrome (Savage’s syndrome)
Premature menopause Autoimmune ovarian failure (Blizzard’s syndrome) Iatrogenic – chemo- and radiotherapy, surgery
Diagnosis - medical history; low E2, elevated FSH and LH levels; E-P test, exogenous Gn
Pathology of the genital outflow tract
Congenital defects of the uterus and/or vagina preventing menstrual bleeding Müllerian anomalies
Lack of the uterus and/or vagina (Mayer-Rokitansky-Kuster-Hauser syndrome)
Imperforate hymen Treatment - surgery
Asherman’s syndrome – scarring of the uterine cavity After dilation and curettage (D&C) Treatment – hysteroscopy; E2
Obstruction of the genital outflow tract – Congenital defects
Amenorrhea - diagnosis Prolactin serum level
Elevated Normal
Negative Positive
Positive Negative
Elevated Decreased
HyperprolactinemiaP
E+P
Obstruction of Genital outflow
FSH level
Anovulation
Ovarian failure
Hypothalamic-Pituitary Dysfunction
Treatment of the amenorrhea Congenital – Isolated hypogonadotropic
hypogonadism – E and P replacement, exogenous GnRH in pulsatile manner
Functional – changing behavior Drugs - Psychogenic causes
Anorexia nervosa Chronic anxiety
Head injury Neoplastic diseases - surgery Prolactin secreting adenoma – bromocriptine Ovarian failure – hormonal replacement Obstruction of the genital outflow tract - surgery
Dysfunctional uterine bleeding
Irregularity without organic pathologyUsually associated with anovulation (periodical ovulation)Causes Hyperprolactinemia PCOD Hyperandrogenism Obesity Early stage of premature ovarian failure Unknown
Irregular, extensive uterine bleeding
Anovulatory cycle
1 5 14 28
E2
21P
ovulation
Dysfunctional uterine bleeding
Chronic estrogen stimulation, unopposed with progesterone
Endometrium outgrows its blood supplyIschemia, necrosisThe endometrium is partially shedIrregular, unpredictable, bleeding The the extent of the bleeding depends on the levels of the estradiol Infrequent and light Frequent and heavy
Elongated mitogenic stimulation without progesterone action
Dysfunctional uterine bleeding
Luteal phase defectThe ovulation existCorpus luteum is poorly developed and
insufficientShortening of the reproductive cycleMenses occur earlier than expected If conception and implantation occur the
function of the corpus luteum is not adequate to support the gestation
Dysfunctional uterine bleeding - diagnosis
Medical history Irregular uterine bleedingLack of premenstrual symptoms
characteristic for ovulatory cycles: Breast tenderness and fullness, abdominal
bloating, mood changes, edema, weight gain, menstrual cramps
Exclusion of the organic causesUterus – leyomioma, infection, polyps,
neoplasmic diseases Cervix – polyps, erosions, carcinomaVagina – carcinoma, injuries, foreign
bodies
Dysfunctional uterine bleeding – diagnosis (cont.)
Confirmation of anovulationBBTUltrasound examinationPeriovulatory painLuteal phase progesterone serum levels
Endometrial biopsy Proliferative endometriumEndometrial hyperplasia
Dysfunctional uterine bleeding - treatment
Termination of the bleeding (treatment of the acute hemorrhage) - hospitalization Administration of progestational agent for 10 days –
secretory changes in the endometrium High doses of estrogen and progestational agent D&C
Establishment of regular cycles (prevention of recurrences) OC progestational agent – 16th-25th day of cycle
Diagnosis and treatment of Hyperprolactinemia, PCOS, Hyperandrogenism, Obesity
HyperprolactinemiaHYPOTHALAMUS
ADRENALS
OVARYOVARIAN STEROIDS
ANDROGENS
Hyperprolactinemia - Causes
Adenoma and microadenoma Prolactinoma Others
Thyroid gland insufficiency – TRH increase Drugs Tranquilizers Antipsychotic (chlorpromazine) GI stimulant (Metoclopramide) Estrogens Methyldopa
Chronic stressInadequate regression after labor
The effects of elevated level of prolactin
Suppressing pulsatile secretion of GnRH
Decrease in Gn levels
Disturbances in cyclic release of LH in response to the positive feedback of estradiol
Decreased ovary sensitivity to Gn – receptors expression
Stimulation of the adrenal androgens release
Hyprprolactinemia - symptoms
Galactorrhea
Delayed menarche
Luteal phase defect
Anovulation
Oligomenorrhea
Primary or secondary amenorrhea
Hyprprolactinemia – diagnosis and treatment
Diagnosis
Prolactin serum levels Basal In dynamic test (MCP, TRH)
CT, NMR
Treatment
Bromocriptine
Surgical treatment
PCOS – polycystic ovarian syndrome
Definition
Chronic anovulation or infrequent ovulation
Androgen excess
Metabolic abnormalitiesHyperinsulinemia (50%) Insulin peripheral tissue resistance
Etiology
Genetic predisposition
Environmental factors
FOH – functional ovarian hyperandrogenism
FAH - functional adrenal hyperandrogenism
PCOS
PCOS
LH
Theca interna stimulation (+)
adrostendion estrone
adipose tissue conversionandrostendione estrone
Clinical SymptomsOligomenorrhea or amenorrheaAcne Hirsutism – excess body hairAppearance of coarse, dark and dense
terminal hair
Obesity (30-50%)Infertility
PCOS
Hyperandrogenism - symptoms
Hirsutism – excess body hairAppearance of coarse, dark and dense
terminal hair
Acne
Virilization – not present in PCOSClitoral enlargementDeepening of the voice Involution of the breastMusculine appearance
Diagnosis
Elevated LH serum level
Increased LH/FSH ratio
Elevated androstendione serum level
Elevated total testosterone serum level
Elevated estrone serum level
Lowered SHBG
Ultrasound – polycystic ovaries, increased volume of ovaries
BMI
PCOS
PCOS
Treatment
OC
Metformin
Androgen receptor antagonist – cyproterone acetate
5-alpha reductase inhibitors - finasterid
FAH – dexametasone (0,25 md/d)
Ovarian stimulation & ovulation induction
Premenstrual syndrome - PMSThe cyclic recurrence during the luteal phase of the
menstrual cycle of a combination of distressing physical, psychologic, or behavioral changes that interfere with family, social, or work-related activities
Premenstrual Dysphoric disorder – regular, cyclic occurrence of depressed mood, marked anxiety, affective lability, decreased interest in activities during the last week before the onset of menses
SymptomsSomatic – breast tenderness and swelling, bloating, constipation or diarrhea, headache, weight gainEmotional – anxiety, irritability, confusion, crying, depression, changes of libidoBehavioral – cravings, increase appetite, poor concentration
PMS - Etiology - theories
Psychiatric cyclic manifestations of psychopathology
Endocrinologic abnormality in letal phase sex steroid levels –
elevated E2, decreased progesterone cyclic occurrence of the symptoms presence of ER and PR in CNS
Endorphin decrease of endorphin levels in the luteal-phase PMS symptoms similar to symptoms of opiate
withdrawal Alleviation of symptoms after excessive exercise
PMS - DiagnosisNo specific historical or physical assessment findings or laboratory markers are diagnostic of PMSCyclic, luteal-phase related, occurrence of the symptomsMenstrual diary – monitoring and recording
of key symptoms and their severity on a daily basis
Symptom-free follicular phaseExclusion of organic or functional pathology
PMS - Treatment
Cooperation of gynecologist, psychiatrist, psychologist, endocrinologistEducation of the patient Diet Fresh fruit and vegetables Minimizing refined sugars and fats Frequent small meals Minimizing salt
ExerciseMedical treatment Induction of anovulation – OC, Danazol, GnRH analogues Progesterone Nonsteroidal anti-inflamatory agents Diuretics Anxiolitic and antidepressant medications
Puberty - physical, emotional, and sexual transition from childhood to
adulthood
Prerequisites
Normal hypothalamus capable of responding to elevated levels of sex steroids by appropriate pulsatile secretion of GnRH
Normal pituitary that is sensitive to GnRH and contains a pool of releasable gonadotropins
Normal ovaries capable of secreting estrogen and progesterone in response to pituitary gonadotropins (FSH, LH)
PubertyThe onset of the pubertal event in each individual is variable and influenced profoundly by genetic and environmental factors The average onset of puberty is between ages 8 and 13 yearsThe events initiating the onset – unknownIncreased maturity of the hypothalamic-pituitary axis – pulsatile GnRH secretionCNS appears to control the onset of puberty – an intrinsic CNS inhibitory mechanism suppressing pulsatile GnRH release Decrease in the CNS inhibitory action increase in pulsatile GnRH release and pituitary responsiveness
Puberty
Adrenarche – at age 8-10 increased secretion of adrenal androgens (DHEA) – pubic and axillary hair growth – precedes the growth spurt by 2 years Maturation of the axis – increase in Gn response to GnRH Prepubertal children – minimal response to GnRH
– small LH response Pubertal children – greater LH response to GnRH
– sleep-associated gonadotropin secretion Development of of cyclic release of LH in
response to the positive feedback of estradiol
Puberty
Event Age Hormone
Breast budding 10-11 Estradiol
Sexual hair growth 10,5-11,5 Androgens
Growth spurt 11-12 GH
Menarche 11,5-13 Estradiol
Adult breast development 12,5-15Progesterone
Adult sexual hair 13,5-16 Androgens
Hyperandrogenism
Sources of the androgens in female Dehydroepiandrosterone (DHEA) – suprarenal
glandsAndrostendion - suprarenal glands; ovariesTestosterone - suprarenal glands; ovaries;
adipose tissue
Functions of the androgens in femalePrecursors of the estrogensStimulate and maintain sexual hair growthResponsible for female libido
Hyperandrogenism - causes
Increased synthesis and release PCOD - ovary and/or adrenal glands Congenital adrenal hyperplasia (21- and 11-
hydroxylase deficiency) Ovarian tumors – Androblastoma, Gynandroblastoma Adrenal adenoma Obesity
Increased expression and/or sensitivity of the androgen receptors in peripherial tissues
Increased 5 reductase activity (TDHT) Constitutional hirsutism
Iatrogenic – glucocorticoids, OC, Danazol
Hyperandrogenism - symptoms
Hirsutism – excess body hairAppearance of coarse, dark and dense
terminal hair
VirilizationAcneClitoral enlargementDeepening of the voice Involution of the breastMusculine appearance
Top Related