Reproductive System Hormones

Hormonal Regulation of the Reproductive System

• The hypothalamus releases gonadotropin-releasing hormone, prolactin releasing/inhibiting hormone, and oxytocin.
• The pituitary gland releases FSH and LH from the anterior pituitary and prolactin and oxytocin from the posterior pituitary in females (F).
• The testes produce testosterone and inhibin.
• The ovaries produce estradiol, progesterone, and inhibin.
• The adrenal cortex produces small amounts of testosterone precursor.

Pathology Due to Dyshormonal Conditions in Ovaries

• Follicle and luteal cysts originate from unruptured ovarian follicles, or follicles that immediately seal after rupturing.
• Complications of ovarian cysts include intraperitoneal bleeding from rupture and increased estrogen production.
• Polycystic ovarian syndrome (Stein Leventhal syndrome) presents with polycystic ovaries, chronic anovulation, menstrual abnormalities, hyperandrogenism, and decreased fertility.

Pathology Due to Dyshormonal Conditions in the Uterus

• Endometrial hyperplasia involves a disordered proliferation of endometrial glands.
• Endometrial hyperplasia is caused by estrogenic stimulation of the endometrium with a progesterone deficiency.
• Failure of ovulation (in perimenopause), prolonged administration of estrogenic steroids, estrogen-producing ovarian cysts or tumors, and obesity can cause endometrial hyperplasia.
• Complications of endometrial hyperplasia include bleeding from the uterus (metrorrhagia), anemia, and progression to adenocarcinoma of the uterus.

Pathology Due to Dyshormonal Conditions in the Breast

• Benign breast disease includes cysts and fibrosis, characterized by increased fibrous stroma and dilatation of ducts and cysts without epithelial proliferation.
• Epithelial hyperplasia can occur with or without atypia, seen as an increase in the layers of the duct-lining epithelium.
• Sclerosing adenosis involves intralobular fibrosis and proliferation of small ductules or acini.
• Fibroadenoma is also considered a benign breast disease.

Benign Prostatic Hyperplasia

• BPH involves prostatic enlargement due to proliferation of stromal and glandular elements.
• Androgen-dependent growth of stromal and glandular elements is crucial to BPH.
• Dihydrotestosterone (DHT) mediates prostatic growth.
• DHT is synthesized in the prostate from circulating testosterone via 5 alpha-reductase type 2.
• DHT binds to nuclear androgen receptors, regulating genes supporting growth of prostatic epithelial and stromal cells.
• The prostate enlarges to 60-100 grams with well-circumscribed nodules.
• Prostatic hyperplasia is classified histologically as glandular, fibromuscular, or mixed.
• BPH complications include compression of the urethra, urocystitis, ascending pyelonephritis, and urosepsis, potentially leading to renal failure and septicopyemia

Carcinoma of the Prostate

• Prostate carcinoma is most commonly (around 95%) adenocarcinoma.
• There may be invasion into adjacent soft tissues like the urinary bladder and rectum.
• Hematogenous metastases often occur in the lungs and bones.
• Lymphogenous spread is typical to paraaortic and pelvic lymph nodes.

Neoplasia of the Cervix Uteri

• Most cervix uteri tumors originate from the epithelium and are caused by HPV.
• Tumors are commonly localized at the junction of columnar mucous-secreting epithelium of the endocervix and the squamous epithelium of the exocervix.
• HPV cancerogenesis begins with precancerous epithelial lesions, known as Squamous Intraepithelial Lesions (SIL).
• Low-grade SIL is associated with HPV but does not progress directly to invasive carcinoma, classified as CIN I (cervical intraepithelial neoplasia).
• High-grade SIL poses a high risk for progression to carcinoma, classified as CIN II and CIN III (Ca in Situ).
• The most common type of neoplasia is squamous cell carcinoma in the exocervix.
• Adenocarcinoma from the endocervix is a less common occurrence.
• Squamous cell carcinoma can be non-invasive (Ca in situ) or invasive.
• Metastases typically spread to inguinal, minor pelvis, and paraaortic lymph nodes.
• Infiltration to the urinary bladder or rectum from the endocervix can lead to fistula uterovesicalis or fistula uterorectalis.

Uterine Tumors

• From smooth muscle cells of the myometrium, benign tumors can be leiomyomas (intramural, submucosal, or subserosal).
• Malignant tumors from the smooth muscle cells of the myometrium results in myosarcoma.
• From the endometrium, benign tumors are endometrial polyps, while malignant ones include adenocarcinoma and chorioncarcinoma.

Breast Carcinoma

• Carcinomas are divided into in situ and invasive types.
• Carcinoma in situ is a neoplasia limited to ducts and lobules by the basement membrane.
• Types of in situ carcinoma include Intraductal, Intraductal carcinoma with Paget disease, and Lobular carcinoma in situ (in terminal ducts and/or ductules).
• Types of Invasive carcinoma are invasive ductal carcinoma (65-80 percent), invasive ductal carcinoma with Paget disease, invasive lobular carcinoma, medullary carcinoma (1-5 perc), and colloid carcinoma.
• Immunohistochemistry is used to test for estrogen receptors, progesterone receptors, and HER2/neu receptors in breast cancer.
• Immunochemistry is also used to predict the potential response to therapy

Spreading of Breast Carcinoma

• Spreading direction depends on the localization of the carcinoma.
• Cancer spreads from outer quadrants to axilla lymph nodes and superior to nodes above the clavicle and neck.
• It can spread from medial quadrants to the other breast and mediastinum, as well as inferior to abdominal viscera.
• Distant metastases by blood can affect all organs.

Classification of Ovarian Neoplasms

• Primary ovarian neoplasms originate in the ovary.
• Metastatic tumors can spread to the ovaries from primary sites: uterus, fallopian tubes, contralateral ovary (organs derived from paramesonephric (or Müllerian ducts), breast, gastrointestinal tract (colon, stomach, biliary tract, pancreas).
• Metastatic gastrointestinal and breast neoplasia to the ovaries is termed Krukenberg tumor.

Primary Ovarian Tumors Classified By Tissue Type

• Tumors derived from surface epithelium (coelomic): Cystadenoma serosum and cystadenocarcinoma (most common), Cystadenoma pseudomucinosum and cystadenocarcinoma pseudomucinosum, Cystoma endometrioidum and Carcinoma endometrioidum, Fibroadenoma, seu neoplasma Brenneri (neoplasma malignum Brenneri) with low hormonal activity if fibroblasts resembling theca cells are in the stroma.
• Sex cord-stromal tumors (hormonally active): Folliculoma, seu neoplasma granulosocellulare (folliculoma malignum), Thecoma (thecoma malignum), and Androblastomas, androblastoma malignum (derived from Sertoli-Leydig cells)..
• Germ cell tumors: Teratomas (dermoid cyst, struma ovarii) derived from totipotential cells. Teratoma malignum, Chorioncarcinoma (derived from trophoblast), and Dysgerminoma (ovarian counterpart of seminoma testis).

Hormonally Active Estrogen-Producing ovarian Neoplasms

• Includes Folliculoma, seu neoplasma granulosocellulare (folliculoma malignum), Thecoma (thecoma malignum), and Fibroadenoma, seu neoplasma Brenneri (neoplasma malignum Brenneri) with low hormonal activity.

Hormone Producing Ovarian Neoplasms

• Androblastomas (Sertoli-Leydig tumor) produce masculinization.

Complications of Ovarian Tumors

• Dyshormonal state depends on the type of tumor.
• Rupture of a cyst can lead to pseudomyxoma peritonei as a result of neoplastic epithelial cell proliferation.
• Malignanization of cystadenomas can occur.
• Massive ascites can result if there is tumor seeding into the peritoneal cavity.
• Intestinal obstruction.
• Cachexia.

Neoplasm Of Testes

• Derived from germ cells: Seminoma, a malignant rapidly metastasizing tumor; embryonal carcinoma; chorioncarcinoma; teratoma.
• Derived from sex cord-gonadal stroma: Interstitial cells (Leydig cells) tumor and androblastoma (Sertoli cells tumor), both hormonally active.