OB/GYN (Menstrual Irregularities)
What are other causes of peripheral "pseudo" precocious puberty?
Congential Adrenal Hyperplasia (CAH) and Adrenal tumors
What is the most common cause of delayed puberty?
Constitutional delay
In PMS/PMDD there are adverse physcial and behavioral symptoms. What are the top physical symptoms?
# 1 - Fatigue #2- Bloating
What is the cause of abnormal uterine bleeding in a Peri-menarchal patient?
- 5-7 yrs after menarche - Immature HPO axis
Why would I check a FSH level if the uterus is present and there is no obstruction?
- Elevation indicates gonadal failure - Low/normal indicates upstream issue
Why does ovulation not occur in Anovulatory Cycles?
- Lots of estrogen, (not cyclically produced) but no corpus luteum, ie no progesterone - "unopposed estrogen"
What usually causes primary amenorrhea?
1) 50% chromosomal abnormalities (gonadal failure) # Turner Syndrome (45,X), other dysgenesis 2) 20% hypothalmatic (The problem starts at the hypothalamus) hypogonadism including functional 3) 15% absence of uterus,cx a/o vag, muller.agen 4) 5% transverse vag septum/imperf. hymen 5) 5% pituitary disease 6) Remaining 5% combination of disorders PCOS (Polycystic ovary syndrome) (, CAH (Congenital Adrenal Hyperplasia), T-Fem( Androgen insensitivity Syndrome)
Other than the classic TRIAD of dysmenorrhea, dyspareunia, and dyschezia, what are other symptoms of endometriosis?
1) Chronic Pelvic Pain 2) Pre or Postmenstrual spottin 3) Infertility
What other diagnosis is endometriosis contributory to?
1) Chronic pelvic pain (CPP) 2) Dyspareunia (painful sexual intercourse) 3) Dysmenorrhea 4) Infertility
What are rare/uncommon causes of primary amenorrhea?
1) Congenital GnRH deficiency (rare) - Kallman's if anosmic 2) Constitutional delay of puberty (uncommon) 3) Hyperprolactinemia (rare) - Frequently accompanied by galactorrhea - Pit adenoma/craniopharyngioma - Prolactin levels >15-20ng/ml o Increased by stress, sleep, exercise, etc
What are other PMS/PMDD therapies that may be efficacious?
1) Continuous OCPs (esp with drospirenone) 2) Exercise and relaxation techniques 3) Agnus castus fruit extract (chasteberry tree) (not FDA regulated) 4) Calcium (1200 mg daily) 5) Vitamins D (1200 mg/day) and B6 (<100 mg/day) 6) Bright light therapy- may be placebo effect
What is the medical therpay for moderate abnormal uterine bleeding?
1) Cyclic estrogens PLUS Progestin (HRT) 2) Oral Contraceptive Pills
What are the 2 widely used diagnostic sets for PMS and PMDD?
1) DSM IV 2) UCSD
What is the classic TRIAD of endometriosis?
1) Dysmenorrhea (painful mensturation) 2) Dyspareunia (painful sexual interourse) 3) Dyschezia (difficulty in defecating)
What is secondary Dysmenorrhea usually associated with?
1) Dyspareunia 2) Infertility 3) Abnormal Uterine Bleeding
What are the surgical options for abnormal uterine bleeding?
1) Endometrial ablation (Provides amenorrhea for 75%) 2) Hysterectomy - TAH (Total abdominal hysterectomy) - TVH (Total vaginal hysterectomy)
What is secondary dysmenorrhea associated with?
1) Endometriosis 2) Fibroids, adenomyosis 3) Ovarian cysts
What are the factors affecting the time of onset of puberty?
1) Genetics-- mother-daughter, sister concordance 2) Nutritional state--? validity of critical body wt (47.8kg) 3) Latitude, altitude, urban/rural all influence onset
What are the 3 classifications of Precocious Puberty?
1) Gonadotropin-dependent PP (Central or "True") 2) Gonadotropin-independent PP (Peripheral or "Pseudo") 3) Incomplete PP
What is the medical therpay for severe abnormal uterine bleeding?
1) High-dose estrogen- Premarin 25mg IV 2) D&C ---> This is the treatment of choice in unstable patients
What are other causes of secondary amenorrhea?
1) Hyperprolactinemia (prolactinoma) - Suppresses GnRH 2) PCOS (Excess androgens are produced. The androgens are converted to estrogen and causes amenorrhea)
What is the work-up in abnormal uterine bleeding?
1) Make sure the bleeding is uterine (because bleeding can be arising form the urethra, bladder, vagina, vulva) 2) Same as amenorrhea 3) Rule out organic causes - H&P - Labs (HGG, TSH, Prolactin Coagulation Studies, Pap Smear) - Studies (Fibroids, poylps, endometrial thickness, endometiral biopsy)
What 2 causes low levels of gonadotropinsand sex steroids during the prepubertal period?
1) Maximal sensitivity of the gondadostat to the negative feedback effect of the low, circulating levels of estradiol 2) Intrinsic central nervous system inhibition of the hypothalamic gonadotropin releasing hormone (gnRH) secretion (More likely since gonadal agenesis patients have same pattern of LH/FSH elevations as normal patients) **These mechanisms occur independent of the presence of functional gonadal tissue
What is the treatment of endometriosis?
1) NSAIDs 2) Cyclic hormones - Progesterone - Oral contraceptive pills 3) Danazol (Androgen analog that inhibits FSH/LH) 4) GnRH agonists (Depo-Lupron ) which acts as a pseudomenopause which will suppress the symptoms of endometriosis if fertility is not a present concern)
What is the preferred treatment of Primary dysmenorrhea?
1) NSAIDs 2) OCP
Who are surgical candiates for Abnormal uterine bleeding?
1) Patient with underlying orgnaic cause 2) Patients who fail medical therapy 3) Consider in patients who have completed child bearing desires
When is it normal to NOT have menses and not classified as Amenorrhea?
1) Pre-pubertal 2) Gravid (pregnant) 3) Lactating 4) Post-menopausal
What are the organic causes of Abnormal Uterine Bleeding?
1) Pregnancy 2) Tumor ---fibroids, polyps, adenomyosis, endometrial Ca 3) Inflammation—cervical, uterine infections 4) Clotting abnormalities—von Willebrand's 5) Disorders of hepatic metabolism—advanced liver disease leading to reduced production of clotting factors 6) IUD 7) Meds---ie ASA, coumadin,exog estrogen
What is the medical treatment of a patient that has abnormal uterine bleeding and is hemodynamiccally stable BUT there is > 1 pad/hr of blood loss?
1) Premarin 2.5mg qid until bleeding subsides then then Add Provera 10 mg daily for last 10 days of cycle or 2) Cascading regimen of OCPs (<1 pad/hr) - 5 pills day 1, 4 day 2, 3 day 3, etc X 1 week - Should have w/d bleed when stopped - May need anti-emetics or 3) Progestin only for younger patients more likely to be sufficiently estrogenized - Provera 10-20 mg bid x 5-10 days
There are two types of Amenorrhea. What are they?
1) Primary 2) Secondary
What are the two categories of delayed puberty?
1) Primary hypogonadism 2) Secondary hypogonadism
What treatments are NOT effective for PMS symptoms?
1) Progestin-only OCPs 2) Conventional use of OCPs 3) Evening Primrose oil 4) Gingko Biloba 5) Essential fatty acids 6) Tricyclic antidepressants/Lithium
What are other SSRIs that are taken for PMS and are very effective?
1) Sertraline 2) Paroxetine 3) Citalopram
What are the contributing factors for Functional Amenorrhea?
1) Stress, eating disorders, excessive exercise 2) Wt loss or wt <10%IBW 3) Celiac disease
What are the signs of endometriosis?
1) Tender adnexal mass (Endometriomas AKA "Chocolate Cysts) 2) Fixed and "Retroverted Uterus" 3) Rectovaginal septum nodules 4) Sharp, firm "barb" on the uterosacral ligament
What are the Endocrine causes of Abnormal Uterine Bleeding?
1) Termed "DUB" 2) Results from anovulation - Factors affecting HPO axis - Systemic diseases (celiac, thyroid,etc) 3) NOT associated with organic pathology 4) Diagnosis of exclusion
What happens as a result of the loss of gonadostat sensitivity and intrinsic CNS inhibition
1) The HPO axis is less responsive and it takes more estradiol (gonadostat) to shut down FSH/LH 2) FSH/LH increase causing follicular maturation which leads to increased sex steroid production
There is clearly genetic predisposition to endometriosis. What are the three theories?
1) The retorgrade menstruation theory 2) The mullerian dysplsia theory 3) The lymphatic spread theory
What are the surgical options in endometriosis?
1) Total abdominal hysterctomy (TAH) with bilateral salpingo-oophorectomy (TVH, BSO) 2) Total vaginal hysterectomy (TVH) with bilateral salpingo-oophorectomy (TVH, BSO)
Premature thelarche and premature adrenarche are of little clinical significance and are associated with appropriate sexual maturation. When would I see peaks of premature thelarche?
2 peaks - one peak at age 2 and another peak at age 6-8
What is the differential for Abnormal Uterine Bleeding?
25% organic *demonstrated pelvic pathology, pre-existing disease, or medication) 75% neuroendocrine dubbed "dysfunctional uterine bleeding-->diagnosis of exclusion (I.e. "can't find anything that is causing this")
What is endometriosis?
A benign condition in which endometrial glands and stroma are present OUTSIDE of the uterine cavity and walls Ectopic endometrial tissue
What can cause Ovarian failure prior to age 30?
A chromosomal abnormality and a karyotype may be considered to look for mosaicism.
What is the mean age of Adrenarche (Pubarche) in African Americans vs. Whites)
AA is 8.8 years Whites is 10.5 years
What is the mean age of thelarche (breast budding) in African Americans vs. Whites?
AA is 8.9 years Whites is 10.0 years
What happens in Functional Amenorrhea?
Abnormal GnRH secretion - Low gonadotropin levels, absent surges, etc - ie non-ovulatory - FSH usually in low/normal range
What is the Most common gyn presenting complaint?
Abnormal Uterine Bleeding
What is the prevailing theory for PMS/PMDD?
Abnormal neurotransmitter response to lutreal hormonal changes - Serotonin likely involved - Gonadal steroids necessary for effect
When should menarche have occured by?
Age 16
This is described the absence of menstrual bleeding
Amenorrhea
Testicular differentiation with male androgens, but lacking receptors, leads to female phenotype. What is this celled
Androgen insensitivity
Lack of GnRH from the hypothalamus may be accompanied by a lack of olfactory development. What is this called?
Anosmia of Kallman's syndrome
This is the Cause of DUB OR amenorrhea - MOST common etiology of secondary amenorrhea after pregnancy is ruled out
Anovulatory Cycles
What is the second most common etiology of secondary amenorrhea (after pregnancy is ruled out)?
Anovulatory cycles
What is the 2nd most common cause of secondary amenorrhea?
Anovulatory cycles - Functional hypothalamic amenorrhea o Weight loss below 10%IBW and exercise o Nutritional deficiencies o Leptin deficiency
This syndrome is caused by uterine synechiae, the result of D&C trauma or inflammation secondary to STD e.g. Chlamydia
Asherman's syndrome
When does the loss of gonadostat sensitivity and intrinsic CNS inhibition occur?
At age 11
When is Anovulatory Cycles most common?
At extremes of menses (JUst starting to have menses or getting ready to stop)
What is another anovulatory agent used to eliminate PMS/PMDD symptoms?
Danazol
What is Dyspareunia associate with?
Deep thrust penetration during intercourse
What if the Uterus/cervix/vagina absent?
Either anomaly or TFem
Breast development? ie ovarian function
Either outlet obstruction (XX, normal testost) or quasi-estrogen (XY, elevated testost--Tfem)
Always start with FSH/LH levels/ What will the FSH/LH levels be in Primary hypogonadism?
Elevated
So who should be treated for endometriosis?
Endometriosis associated with: 1) Pelvic Pain 2) Dysmenorrhea 3) Dyspareunia 4) Abnormal bleeding 5) Ovarian cysts 7) Infertility due to gross distortion of tubal and ovarian anatomy
What is the name for the hypothalamic-pituitary-gonadal system regulating gonadotropin release called?
Estradiol (Gonadostat)
What is peripheral "pseudo" precocious puberty caused by?
Excess secretion of sex steroids
If there are NO secondary sexual characteristics, then there is no product from the ovaries; either the ovaries are not being stimulated, or there are no ovaries e.g. if FSH is high, then there is no ovarian feedback, what should I do?
Feedback—obtain karyotype to diagnose genetic defect (45X-Turner's, mosaic, etc)
Who gets precocious puberty more. Male or Females?
Females
What SSRI gives significant symptom improvment and is taken during the luteal phase of the cycle?
Fluoxetine
What is the MOST COMMON cause of peripheral "pseudo" precocious puberty?
Functional Ovarian Cysts (Remember Peripheral "Pseudo" precocious puberty is INDEPENDENT of Gonadotropin)
What anovulatory agent are added with estrogen and progesterone "add bacl" and are effective in eliminating PMS/PMDD symptoms?
GnRH (Leuprolide)
Ok so the association of PMS with follicular and luteal phases invokes the necessity of an ovulatory event. What does this mean?
If the patient is not ovulating, she does NOT have PMS
What does a Lack of menarche with simultaneous development of other secondary sexual characteristics imply?
Implies lack of source or outlet for menstrual contents.
Where does endometriosis MOST commonly occur?
In the dependent portions of the pelvis
Is peripheral "pseudo" precocious puberty isosexual?
It can be isosexual or contra-sexual meaning there is virilization
What cause central "true" precocious puberty?
It is Gonadotropin-dependent 80% Idiopathic 20% From CNS causes
What causes true precocious puberty?
It is caused by early maturation of the HPO axis
What is Functional Amenorrhea?
It is non-pathologic
When should menarche never occur before?
It should never occur before age 9
How long does it take to go through puberty?
It usually occurs over a 3 year period
In PMS/PMDD there are adverse physcial and behavioral symptoms. What is the top behavioral symptom?
Labile mood
What consstitutes delayed puberty?
Lack of thelarche by age 12
What is the cause of abnormal uterine bleeding in a Reproductive patient?
Less cycle variability ages 20-40
Always start with FSH/LH levels/ What will the FSH/LH levels be in Secondary hypogonadism?
Low or normal
This theory suggests that endometrial tissues are taken up into the lymphatics draining the uterus and transported to various pelvic sites where the tissue grows ectopically
Lymphatic spread theory
This frequent menstrual bleeding that is excessive and irregular in amount and duration.
Menometrorrhagia
This is prolonged or excessive uterine bleeding that occurs at REGULAR intervals (more strictly 80ml or more of blood loss per menstrual cycle or bleeding greater than 7 days)
Menorrhagia
This is IRREGULAR menstrual bleeding or bleeding between periods
Metrorrhagia
This theory proposes that endometriosis results from the metaplastic transformation of peritoneal mesothelium into endometrium under the influence of certain, generally unidentified stimuli
Muellerian dysplasia theory
Is there a serum marker for PMS/PMDD?
NO
Are there vitamin or mineral deficiencies proven in PMS/PMDD?
No
Is there a relationship between the stage of endometriosis and the frequency and severity of pain symptoms?
No
Is peripheral "pseudo" precocious puberty gonadotopin dependent?
No it is gonadotropin INDEPENDENT
Are there significant side effects of SSRIs?
No they are usually mild and self limiting only causing sexual dysfunction and ininsomnia
Central "True" precocious puberty responds to GnRH. Does peripheral "pseudo" precocious puberty resond to GnRH?
No. FSH/LH is suppressed and does not respond to GnRH
Is ultrasound recommneded in endometriosis?
Nope. It lacks sensitivity
What is the medical therapy for mild abnormal uterine bleeding?
Observation and Expectant Management
Who usually gets secondary dysmenorrhea?
Older patients
This is menses occuring at intervals >35days
Oligomenorrhea
Is Amenorrhea a diagnosis or symptom?
Pathologic symptom (not a diagnosis)
Who is Surgical ablation or excision required for?
Patients with infertility
What is the cause of abnormal uterine bleeding in a Peri-menopausal patient?
Peri-menopausal—declining ovarian function - Fibroids, polyps, endometrial Ca
What is premature adrenarche a risk factor for?
Polycystic ovarian syndrome (PCOS)
This is frequent menstrual bleeding (more strictly regular bleeding that <24days)
Polymenorrhea
What happens by mid puberty?
Positive mechanisms mature -Increased estradiol causes decreased LH
This is Appearance of ANY secondary female sex characteristics prior to age 8 (2.5 standard deviations less than the expected age of pubertal onset)
Precocious puberty
What is the most common cause of secondary amenorrhea?
Pregnancy
This is defined as ovarian failure prior to age 40-injury from surgery, radiation, chemotherapy, galactosemia and autoimmunity.
Premature ovarian failure
This is the appearance of a SINGLE secondary sexual characteristic. What is an example?
Premature thelarche (the appearance of breast development before the age of 4) unilateral or bilateral that resolves spontaneously within months and that is secondary to transient estradiol secretion *Usually a normal variant
This is described as the following: - No menses by age "16" in the presence of NORMAL secondary sexual characteristics - No menses by age 13 in ABSENCE of secondary sexual characteristics - No menses within 2 years of thelarche
Primary Amenorrhea
This type of dysmenorrhea is described as the following: 1) Occurs during ovulatory cycles 2) Starts within 6-12 months menarche 3) Related to uterine ischemia/contractions 4) Increased prostaglandin levels 5) Starts within 48-72 hrs of menses
Primary Dysmenorrhea
What do both the DSM-IV and USCD use in the evaluation of PMS/PMDD?
Prospective documentation of signs and symptoms
This is the development of secondary sexual characteristics and reproductive capability
Puberty
What should be given to patients that experience PMS and have bloating?
Reassurance and Diuretics
What is the hallmark for diagnosis Premenstural Syndrome (PMS/ Pre-menstrual Dysphoric Disorder (PMDD)?
Regular ovulatory cycles cause dysfunction of other organ systems
This theory is that endometrial fragments that are transported through the fallopian tubes at the time of menstruation implant and grow in the various intra-abdominal sites causing obstruction
Retrograde menstruation
This is described as the following: Absence of menses for at least 6 months in women who were previously menstruating
Secondary Amenorrhea
This syndrome is pituitary necrosis secondary to post-partum hypotension, e.g. blood loss.
Sheehan's syndrome (Post partum pituitary necrosis)
Ok so if medical therapy for endometriosus does not work, then what?
Surgical ablation or excision
How is the diagnosis of PMS/PMDD made?
Symptoms during the luteal phase and a symptom free period of AT LEAST 7 days in the 1st half cycle for at least 2 cycles
What should the diagnosis of endometriosis be based on
The history of an afebrile patient with the characteristic triad of pelvic pain, a firm, fixed tender adnexal mass, and tender nodularity in the cul-de-sac and uterosacral ligaments
What does increased sex steroids (estradiol/androgens) cause?
The initiation of puberty - Secondary sex characteristics 1) Thelarche 2) Adrenarche 3) Linear Growth 4) Menarche
T or F Large % of patients have "mixed" with anov/ovul cycles
True
T or F. 2 out of three women with endometriosis have ovarian involvment
True
T or F. About 1/2 of ALL women experience dysmenorrhea
True
T or F. In PMS/PMDD, there is a substantial overlay with primary psychologic/psychiatric disorders
True
T or F. In both PMS and PMDD, patiens experience adverse physical, psychologic, and behavioral symptoms during the LUTEAL phase of the menstrual cycle
True
Of the DSM-IV and the UCSD criteria, which one requires the presence of "PHYSICAL (Somatic)" symptoms?
UCSD
Of the DSM-IV and the UCSD criteria, which one uses the a Calendar of Premenstrual Experiences (COPE) as a diagnostic tool?
UCSD
During peri-and post-menopause, what is the MOST worrisome for endometrial cancer?
Uterine Bleeding
What is involved in Dyschezia?
Uterosacral, Cul-de-sac, and retrograde colon involvement
What is the treatment of endometriosis in patients with minimal symptoms or patients that are perimenopausal?
Watchful waiting
How is precocious puberty treated?
With GnRH
What is a typical patient with endometriosis?
Women in her 30's, nulliparous, infertile
What population of people is endometroisis common in?
Women in their 30's
Can Functional Amenorrhea be a source of secondary amenorrhea?
Yes
Is endometriosis estrogen dependent?
Yes
Does Precocious puberty usually follow the normal sequence of development?
Yes (Just early)
Is central or "true" precocious puberty Isosexual?
Yes (the phenotype= the genotype)
What is the cause of abnormal uterine bleeding in a Post-menopausal patient?
BE WORRIED! During peri-and post-menopause, uterine bleeding is MOST worrisome for endometrial cancer
Isolated thelarche may occur prior to age 8 years (as early as age 6) but should be observed carefully for adrenarche. Why?
Because if pubic hair growth does occurs we must be concerned for precocious puberty
Why is the prevalence of of PMS/PMDD overestimated?
Because of the lack of diagnostic criteria
What are the downsides of GnRH agonists such as Depo-Lupron?
Because they induce a pseudomenopause, they may cause hot flashes, other menopausal like side effects and vaginal dryness *They are alos costly
At what ages is the hypothalamic -pituitary-gonadal (HPO) axis suppressed?
Between ages 4-10
What is the definitive diagnosis of endometriosis?
Biopsy (Laparoscopy)
What is necessary to rule out precocious puberty?
Bone age
How is puberty measured?
By using Tanner staging
What should be done in incomplete precocious puberty?
Check the bone age. If there is no acceleration of growth, then there is no treatment needed
What is the cause of abnormal uterine bleeding in a Pre-pubertal patient?
think bleeding defects
