Honnold Reproductive Lecture (Draft)

Delayed Puberty

-Female → no breast development by age 13

-Increased risk for inadequate skeletal development/mineralization

-Psychosocial implications'

-Often due to physiologic (constitutional delay) → maturation is happening, just very slowly.

• Hormone levels are normal, HPG axis intact.

Precocious puberty

-Puberty occurs too early

-3 types:

• Central precocious → GnRH dependent

• Peripheral precocious → GnRH independent

• Benign Precocious → neither

-Results in premature closure of growth plates in long bones → lifelong short stature → profound psychosocial consequences.

Dysmenorrhea

Primary/Secondary amenorrhea

Abnormal Uterine bleeding (AUB)

Polycystic ovary syndrome (PCOS)

Premenstrual syndrome (PMS)

Premenstrual dysphoric disorder (PMDD)

What are the hormonal and menstrual alterations of the female reproductive system?

Dysmenorrhea

Painful menstruation, typically involving abdominal cramps.

Primary Dysmenorrhea

Recurrent, Painful menstruation, NO pelvic disease.

• Excessive PG in ovulatory cycles → myometrial stimulant and vasoconstrictor.

• Onset → a few days before menstruation and persists 48-72 hrs.

-Risk factors:

• Women > 30

• Have not given birth

• Hx of sexual assault, PMS, or sterilization

• Heavy tobacco/alcohol users

• Family history

• BMI < 20

Secondary Dysmenorrhea

Painful Menses WITH pelvic pathologic condition.

• Manifests later in reproductive years.

• May occur anytime in the menstrual cycle

• Associated with endometriosis, and all the other pelvic disorders.

Primary Amenorrhea

Failure of menarche and absence of menstruation by age 14 without secondary sex characteristics.

• Or absence of menstruation by 16 years of age regardless of secondary sex characteristics.

-Common causes;

• Anatomic defects

• Elevated FSH → ovarian failure

• Hyperprolactinemia → prolactin inhibits GnRH

• Hypothalamic amenorrhea → lack of GNrH secretion

• PCOS

Secondary Amenorrhea

Cessation of previous menses for more than 3 months (regular cycles) or 6 months (irregular cycles)

• Common during early adolescence, pregnancy, lactation, and perimenopausal period.

• Hypothyroidism, hyperprolactinemia, excessive exercise/stress/weight loss, PCOS.

Abnormal uterine bleeding (AUB)

Bleeding that is abnormal in duration, volume, frequency, or regularity.

• < 21 days between or > 35 days between

• Duration > 7 days

• Has been present for the majority of 6 months.

Structural causes

• Polyp

• Adenomyosis

• Leiomyoma

• Malignancy and hyperplasia

Non-structural causes:

• Coagulopathy

• Ovulatory dysfunction

• Endometrial

• Iatrogenic

• Not yet classified.

-Mostly associated with lack of ovulation.

Polycystic ovarian syndrome (PCOS)

One of the most common endocrine disturbances affecting women.

• Hyperandrogenic state: cardinal feature

-Diagnostic criteria:

• Ovulatory dysfunction (menstrual irregularity)

• Hyperandrogenism

• Polycystic ovarian morphology

-Polycystic ovaries DO NOT have to be present, and their presence DOES NOT establish diagnosis

-Pathophysiology of hormone imbalance, insulin resistance/hyperinsulinemia and hyperandrogenic state.

premenstrual disorders

Premenstrual syndrome (PMS): Experience at least one physical and one emotional symptom.

Premenstrual dysphoric disorder (PMDD): A severe form of PMS involving at least 5 emotional and physical symptoms.

• Anger, irritability, anxiety, depression.

-Cyclic recurrence (luteal phase) of distressing physical, psychological, or behavioral changes that impair interpersonal relationships or interfere with activities.

• Symptoms being after ovulation.

Pelvic inflammatory disease (PID)

An acute inflammatory process caused by an infection.

• causes scaring and other issues.

• May involve any or all organs in the upper genital tract → uterus, fallopian tubes, or ovaries.

• Typically an ascending infection → spread from lower genital tract.

-Salpingitis → inflammation of the fallopian tubes

-Oophoritis → inflammation of the ovaries.

-Most severe form affects the entire peritoneal cavity.

-Etiology: most often caused by STI

• Chlamydia - Chlamydia trachomatis

• Gonorrhea - Neisseria gonorrhoeae

Vaginitis

Irritation or inflammation of the vagina caused by infection, irritants, pathologies, disruption of normal flora.

• Most common causes:

  • Overgrowth of normal flora → candida albicans

  • STIs → Trichomoniasis, HSV infection

  • Vaginal irritation due to low E2 during menopause → atrophic vaginitis.

-Pathophysiology: Alteration in vaginal environment

• Local defense mechs. → skin integrity, immune reaction

• Vaginal pH affected by → semen, douches, soaps, spermicides.

• Antibiotics → destroys normal vaginal flora → overgrowth of C. albicans.

Cervicitis

Inflammation of the cervix.

• purulent or mucopurulent discharge from the cervical os

• AND/OR endocervical bleeding

-Infectious (most common) → younger, sexually active due to STI

• Chlamydia (C. trachomatis), Neisseria (N. gonorrhoeae).

-non-infectious → older women

• Typically irritation from abnormal vaginal flora due to low vaginal E2

Pelvic organ prolapse

The descent of one or more of the pelvic organs

• Vaginal wall

• Uterus

• Appendix of the vagina

• Bladder/rectum

-Causes

• Trauma

• Constipation

• Pelvic floor surgery

• Damage to the pudendal nerve

• Cancer

• Obesity

Structural alterations

uterine prolapse: The descent of the cervix or entire uterus into the vaginal canal

• Can protrude from vaginal opening

Cystocele: Descent of portion of the posterior bladder wall and trigone into the vaginal canal.

• AKA anterior compartment prolapse

• Usually caused by childbirth

Rectocele: Bulging of the rectum and posterior vaginal wall into the vaginal canal

• AKA posterior compartment prolapse.

Enterocele: A herniation of the rectouterine pouch into the recotvaginal septum.

Benign Ovarian Cysts

-Most common during the reproductive years

• Typically unilateral; random or recurrent events.

• 5-6cm in diameter; can be up to 8-10cm

• Usually asymptomatic

-Follicular cysts: Dominant follicle fails to rupture or 1+ dominant follicles regress

• Fluid-filled, may be absorbed or regressed.

-Corpus luteum cysts: Formed from the granulosa cells left behind after ovulation.

• Highly vascularized, hemorrhagic cysts

• Less common, cause more symptoms.

Endometrial Polyps

-A benign mass of endometrial tissue that contains a variable number of glands, stroma, and blood vessels.

• Usually solitary and structurally diverse

• Seen at any age, often 40-50.

-Risk Factors: Old age, Obesity, nulliparity, early menarche or late menopause, estrogenic states, HTN, diabetes.

-Common cause of intermenstrual bleeding, excessive menstrual bleeding, suboptimal fertility.

Leiomyomas

-Commonly called myomas or uterine fibroids.

• Slow-growing tumor of myometrial smooth muscle

• Most common benign tumor of the uterus

• Most are small and asymptomatic.

-Risk factors: black, age, FH, Nulliparitiy..

-Mutation in MED12 gene common

-Tumor growth → ischemia → necrosis/degeneration → vaginal bleeding.

Adenomyosis

-Prescence of endometrial tissue within the uterine myometrium

• Tissue DOES NOT respond to cyclic hormone changes.

-Risk factors: Increased estrogen exposure, Prior uterine surgery.

-unknown mech.

• Adenomyosis → increased PGs → dysmenorrhea

• Adenomyosis → increased vascularization, abnormal uterine contractions → heavy menstrual bleeding.

Endometriosis

-The presence of functioning endometrial tissue outside of the uterus. (ectopic endometrium)

• Most common location is on the ovaries

-Most common cause of chronic pelvic pain

• 3rd most common reason for hysterectomy

• Higher risk for infertility and cancer

-Pathology:

• Growth depends on E2! Endometrial remodeling is a cyclical process affected by the E2 blood supply and the presence of glandular and stromal cells.

Stage 1: 1-5 points, superficial lesions

Stage 2: 6-15 points, some deep lesions

Stage 3: 16-40 points, minor adhesions, endometrioma.

Stage 4: >40 points, severe adhesions w/ bowel and bladder involvement. severe damage to the pouch of Douglas.

Cervical cancer

-4th most common cancer

-Caused by HPV

• HPV-16, HPV-18

-HPV infects cells and causes mutation with p53 gene → uncontrolled proliferation

Endometrial cancer

-6th most common cancer.

-Risk factor: prolonged exposure to unopposed E2.

• This leads to constant stimulation of the endometrium.

• P4-R inhibits this, when dysfunctional → endometrial hyperplasia.

Ovarian cancer

-7th most common cancer

-5 year survival rate < 45%

-Risk factors: positive FH of breast or ovarian cancer

-Pathophys.

• Most cases → sporadic acquired somatic mutations (TP53 gene)

-Tumors arise from 3 ovarian components

• Can be benign or malignant

• (60%) Epithelial cells →cover the ovary

• (30%) Germ cells → endoderm → oocytes

• (8%) Sex cord/stromal cells → hormone-producing cells.

Proliferative Breast lesions without atypia

Proliferation of ductal epithelium or stroma or both, without cellular signs of abnormality (atypia)

• Usual ductal hyperplasia

• Intraductal papillomas

• Diffuse papillomatosis

• Sclerosing adenosis

• Radial scar (RS)

• simple fibroadenomas

Proliferative breast lesions with atypia (atypical hyperplasia)

-Proliferation of ductal epithelium or stroma or both, with cellular signs of abnormality (atypia)

• Associated with moderately increased risk or breast cancer

• Atypical ductal hyperplasia (ADH)

  • abnormal proliferation fo ductal epithelium

• Atypical lobular hyperplasia (ALH)

  • Abnormal proliferation of lobular units.

Breast Cancer

-Second most common cancer in american females

-BRCA1 and BRCA2 → most important dominant genes.

• Most develop due to DNA damage and genetic mutations.

-Most breast cancers are adenocarcinomas and first arise from ductal/lobular epithelium as carcinoma in situ (CIS)

• Ductal carcinoma in situ (most common)

• Lobular carcinoma in situ

Disorders of the Urethra

Urethritis: inflammation of the urethra

• STI most common → gonococcal urethritis (N. gonorrhoeae)

Urethral strictures → narrowing of the urethra

• Most result from injury to surrounding tissue.

• Iatrogeneic is most common

Disorders of the Penis

_{Phimosis/Paraphimosis: Disorders in which the foreskin (prepuce) is “too tight” to move easily over the glans.}

Phimosis: Foreskin cannot be retracted back over the glans. (hoodie mode)

• Poor hygiene and chronic infections are common causes

Paraphimosis: Foreskin is retracted and cannot be moved forward to cover the glans

Peyronie disease (PD): a progressive non-malignant disorder that results in abnormal curvature when erect.

• Hallmark is tunical fibrosis of the corpora cavernosa (plaque formation)

Disorders of the scrotum/testes

Varicocele: dilated tortuous veins of the pampiniform plexus.

• Sperm may be comprised in structure, function, and numbers.

Hydrocele: Abnormal collection of fluid between the layers of the tunica vaginalis

• In a sac in front of the testes

Testicular torsion: occurs when a testicle rotates, twisting the spermatic cord and interrupting its blood supply.

Ochitis: acute inflammation of the testes.

• usually viral → mumps and rubella

Epididymitis: Inflammation of the epididymis

• most common cause of scrotal pain in adults.

• Elderly → Retrograde flow of urine

• Young males → STI

  • Gonorrhea, chlamydia

Cryptorchidism

Failure of testes to descend through the inguinal canal into the scrotum

• Absence of at least one testicle from the scrotum.

• Most common birth defect of the male genitalia

Testicular cancer

-Most common solid malignancy in young adult men.

-cryptorchidism is most important risk factor !

• also HPV and other viruses can cause it

-Classification:

• Germ cell neoplasia in situ (GNIS

• Derived from GNIS

• Germ cell tumors unrelated to GNIS

Disorders of the Prostate gland

Benign prostatic hyperplasia (BPH): Nonmalignant growth or hyperplasia of prostate tissue.

• NOT a premalignant lesion

• Common cause of lower urinary tract symptoms.

• Most common disease in men >50

Prostatitis: Inflammation of the prostate gland.

• Cat I → acute bacterial

• Cat II → chronic bacterial

• Cat III → chronic prostatitis/Chronic pelvic pain syndrome

• Cat IV → Asymptomatic inflammatory prostatitis

Prostate cancer

-2nd most common cancer in men

• >95% are adenocarcinomas, occuring in the periphery of the prostate.

• Black men and FH are higher risk