The mechanism varies depending on the cause and whether the defect is structural, hormonal, or both. Women who have adequate estrogen levels but a progesterone deficiency don’t ovulate and are thus infertile. In primary amenorrhea, the hypothalamic-pituitary-ovarian axis is dysfunctional. Because of anatomic defects of the central nervous system, the ovary doesn’t receive the hormonal signals that normally initiate the development of secondary sex characteristics and the beginning of menstruation.

Secondary amenorrhea can result from any of several mechanisms, including:

Breast cancer occurs more commonly in the left breast than the right and more commonly in the outer upper quadrant. Slow-growing breast cancer spreads by way of the lymphatic system and the bloodstream, through the right side of the heart to the lungs, and eventually to the other breast, the chest wall, liver, bone, and brain.

Most breast cancers arise from the ductal epithelium. Tumors of the infiltrating ductal type don’t grow to a large size, but metastasize early (70% of breast cancers).

Breast cancer is classified by histologic appearance and location of the lesion, as follows:

The descriptive terms should be coupled with a staging or nodal status classification system. The most commonly used staging system is the TNM (tumor size, nodal involvement, metastatic progress).

Breast tissue appears to respond to hormonal stimulation, although the exact mechanism is unknown. Fibrocystic breast changes involve three types: cystic, fibrous, and epithelial proliferation. Cysts, fluid-filled sacs, are the most common feature and are easily treated. Fibrous tissue increases progressively until menopause and regresses thereafter. Epithelial proliferation diseases include structurally diverse lesions, such as sclerosing adenosis and the lobular and ductal hyperplasias.

Preinvasive disease ranges from mild cervical dysplasia, in which the lower third of the epithelium contains abnormal cells, to carcinoma in situ, in which the full thickness of epithelium contains abnormally proliferating cells. Other names for carcinoma in situ include cervical intraepithelial neoplasia and squamous intraepithelial lesion. Preinvasive disease detected early and properly treated is curable in 75% to 90% of cases. If preinvasive disease remains untreated (and depending on the form

in which it appears), it may progress to invasive cervical cancer. In invasive carcinoma, cancer cells penetrate the basement membrane and can spread directly to contiguous pelvic structures or disseminate to distant sites by lymphatic routes.

In almost all cases of cervical cancer (95%), the histologic type is squamous cell carcinoma, which varies from well-differentiated cells to highly anaplastic spindle cells. Only 5% are adenocarcinomas.

A prevalent but still unsubstantiated theory links undescended testes to the development of the gubernaculum, a fibromuscular band that connects the testes to the scrotal floor and probably helps pull the testes into the scrotum by shortening as the fetus grows. Normally in the male fetus, testosterone stimulates the formation of the gubernaculum. Thus, cryptorchidism may result from inadequate testosterone levels or a defect in the testes or the gubernaculum. Because the undescended testis is maintained at a higher temperature, spermatogenesis is impaired, leading to reduced fertility.

In ectopic pregnancy, transport of a blastocyst to the uterus is delayed and the blastocyst implants at another available vascularized site, usually the fallopian tube lining. Normal signs of pregnancy are initially present and uterine enlargement occurs in about 25% of cases. Human chorionic gonadotropin (HCG) hormonal levels are lower than in uterine pregnancies.

In most cases, uterine cancer is an adenocarcinoma that metastasizes late, usually from the endometrium to the cervix, ovaries, fallopian tubes, and other peritoneal structures. It may spread to distant organs, such as the lungs and the brain, through the blood or the lymphatic system. Lymph node involvement can also occur. Less common are adenoacanthoma, endometrial stromal sarcoma, lymphosarcoma, mixed mesodermal tumors (including carcinosarcoma), and leiomyosarcoma.

The ectopic endometrial tissue responds to normal stimulation in the same way as the endometrium, but less predictably. The endometrial cells respond to estrogen and progesterone with proliferation and secretion. During menstruation, the ectopic tissue bleeds as does the endometrium, which causes inflammation of the surrounding tissues. This inflammation causes fibrosis, leading to adhesions that produce pain and infertility.

Upon stimulation, chemicals are released in the brain that cause signals to pass down the spinal cord and outward through special nerves into the penis. These nerves release another chemical (nitric oxide) that causes the smooth muscles of the penis to relax and blood to rush into the erectile bodies, causing erection. Neurologic dysfunction results in lack of the autonomic signal and, in combination with vascular disease, interferes with arteriolar dilation. The blood is shunted around the sacs of the corpus cavernosum into medium-sized veins, which prevents the sacs from filling completely. Also, perfusion of the corpus cavernosum is initially compromised because of partial obstruction of small arteries, leading to loss of erection before ejaculation.

Anxiety or fear can prevent the brain signals from reaching the level required to induce erection. Medical conditions can block the erection arteries or cause scarring of the spongy erection tissue and prevent proper blood flow or trapping of blood and, therefore, limit the erection.