Ch 25- Alterations of Female Reproductive System

• Chapter 25 discusses alterations of the female reproductive system, including uterine tumor types, puberty, amenorrhea, PCOS, endometriosis, and cervical cancer.

Uterine Tumor Types (Leiomyomas)

• Leiomyomas are benign smooth muscle tumors in the myometrium.
• They are the most common benign uterine tumors, affecting 70-80% of women.
• Most leiomyomas are small, asymptomatic, and clinically insignificant.
• Prevalence increases in women aged 30-50, then decreases with menopause.
• The cause is unknown, but size is related to estrogen, progesterone, growth factors, angiogenesis, and apoptosis.
• Can occur in the fundus of the uterus, in multiples, or singly.
• Classified as subserous, submucous, or intramural based on location in the uterine wall.
• Clinical manifestations include abnormal uterine bleeding, pain, and pressure.
• Can distort the uterine cavity and increase the uterine surface area, leading to increased bleeding.
• Evaluation includes bimanual examination, uterine enlargement, and pelvic sonography or MRI.
• Treatment depends on symptoms, tumor size, age, reproductive status, health, and patient preference.

Puberty in Girls and Boys

• Puberty is the onset of sexual maturation, different from adolescence which is the stage between childhood and adulthood.
• Girls typically begin puberty around 8-9 years with thelarche (breast development).
• Boys typically begin puberty around 11 years, with increased weight and BMI.
• Timing is influenced by genetics, environment, ethnicity, health, and nutrition.
• Reproductive maturation involves the hypothalamic-pituitary-gonadal (HPG) axis, CNS, and endocrine system.
• Hormonal events promote sexual maturation as puberty approaches.
• About a year before puberty in girls, there is an increase in the gonadotropin secretion (LH, FSH) and responsiveness to GnRH.
• Gonadarche stimulates estradiol secretion in girls and testosterone secretion in boys.
• Estradiol causes thelarche, maturation of reproductive organs, and fat deposit in hips.
• Estrogen and increased growth factor production cause rapid skeletal growth in boys and girls.
• Testosterone causes growth of testes, scrotum, and penis with gonadotropins stimulating the gonads.
• The testes produce mature sperm with the ovaries releasing mature ova.
• Male puberty completes with the first ejaculation while female puberty completes with the first ovulatory menstrual period.
• Adrenarche is increased production of adrenal androgens which occurs prior to puberty and results in axillary and pubic hair growth and odor.
• Puberty completes when a person can reproduce.

Delayed Puberty in Girls

• Defined as a lack of clinical signs of puberty by age 13.
• Clinical diagnosis is made without menarche age 15 or 16.
• Risks include psychosocial implications, skeletal development, and mineralization.
• Estrogen is important for bone density.
• Physiologic delay is when hormonal levels are normal, and the HPG axis is intact, but maturation is slow
• This type of delayed puberty tends to be familial.
• 30% of girls with delayed puberty later progressed through normal puberty.
• Treatment involves expectant management or hormone therapy to promote pubertal development and mineralization.
• Functional hypogonadotropic hypogonadism makes up 19% of delayed puberty cases.
• Functional hypogonadotropic hypogonadism is due to an underlying condition unrelated to gonadal function.
• Correction of the underlying issues is the treatment.
• Human gonadal function requires luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
• Disruption in the HPG axis is caused when their releases are regulated by pulsatile secretion of GnRH.
• The GPR54 has been named the gatekeeper gene for activation of the GnRH axis and may require synthetic GnRH or hormone administration.

Delayed Puberty in Boys

• Defined as no clinical signs of puberty by age 14.
• Early diagnosis/treatment is recommended due to potential for sexual immaturity and self esteem issues.
• Physiologic delay is when hormonal levels are normal and the hypothalamic-pituitary-gonadal (HPG) axis is intact, but maturation is happening slowly.
• Physiologic delay is difficult to distinguish from isolated gonadotropin deficiency, it is diagnosed retrospectively.
• Treatment is expectant management to promote pubertal development and mineralization.
• Treatment is correction of the underlying condition.
• Functional hypogonadotropic deficiency can be caused CNS defects, GPR54 mutations, hemochromatosis, hypopituitarism, and marijuana use.
• Chronic conditions cause disruption to the hpg axis.
• Evaluation should target delayed puberty causes that require lab work to measure thyroid function and serum levels.

Obesity and Early Puberty in Females

• Early puberty and obesity in girls could correlate due to higher estrogen levels which stimulate gonadotropin and estrogen secretion.
• Girls with too little body fat and intense exercise may have a delayed maturation while leptin plays an important role in puberty onset.

Polycystic Ovary Syndrome (PCOS)

• The most common cause of anovulation and ovulatory dysfunction and is associated with metabolic dysfunction and is defined by the presence of irregular ovulation and elevated androgen levels.
• A strong genetic link is suspected.
• Hyperandrogenic state is a cardinal feature.
• Clinical manifestations usually appear within 2 years of puberty with commonly known symptoms of obesity, hirsutism, menstrual disturbance, amenorrhea, hyperandrogenism, and infertility.
• Treatment involves reversing/stabilizing estrogen levels, androgen excess menstrual cycles and associated disturbance through combined oral contraceptives, Metformin, diet and exercise and lifestyle changes.

Endometriosis

• Endometriosis is the presence of functioning endometrial tissue outside the uterus.
• The cause is unknown, but the risk is greater for cancers especially in the ovarian area.
• Endometrial cells may implant during retrograde menstruation impaired immunity, and spread through the lymphatic or vascular systems.
• The ectopic endometrium proliferates similar to a normal menstrual cycle.
• Inflammation from cellular inflammatory mediators may lead to fibrosis, scarring, adhesions, and pain.
• Endometrial implants occur in the ovaries, uterine ligaments, and pelvic peritoneum.
• Family history, menstrual abnormalities, never giving birth raise concerns about endometriosis.
• Degree of invasiveness based on findings from different stages like minimal, mild, moderate from laparoscopic images.
• The goal of treatment involves the following: treating pain, stopping progression of symptoms, restoring fertility.
• Can be treated with suppression of ovulation or conservative surgical treatment.

Cervical Intraepithelial Carcinoma (CIN) and Cervical Cancer

• Cervical cancer is caused by cervical human papillomavirus (HPV) infection.
• Precancerous dysplasia is called cervical intraepithelial carcinoma (CIN) and cervical carcinoma in situ (CIS).
• Cervical dysplasia can be identified through examination of cervical cells, and treatment is available to prevent the spread of cancer.
• Infection with high risk HPV is an important part of the development of cervical dysplasia.

BRCA1 Gene

• Most breast cancer occurs in women older than 55, however those younger than 45 may have a risk due to relatives with the sickness, Jewish heritage, radiation treatment, and breast health problems.
• BRCA1 is located on chromosome 17, is a tumor-suppressor gene therefore can be cause for uncontrolled cell growth.
• A family history of both breast cancer and ovarian cancer increases the risk that an individual with breast cancer carries a BRCA1 mutation.
• Carriers are at high risk for ovarian cancer.
• Risks are not equal in carrier.