Epidemiology and symptoms

Age is a risk factor for BPH. Data suggesting that black race puts men at increased risk appear to be poorly controlled for socioeconomic status and access to health care.

BPH causes urethral obstruction severe enough to warrant medical intervention in about 30% of elderly men. Interestingly, the overall size of the prostate does not correlate with either the presence or the severity of outflow obstruction. The fibromuscular hypertrophy that occurs with BPH can partially denervate prostatic and surrounding tissues, leading to urethral irritation and producing frequency and urgency of micturition, urge incontinence and nocturia.

BPH is characterized by a gradual increase in both the glandular and fibromuscular tissue in the periurethral and transition zones of the prostate that surround the urethra at its origin from the bladder and midsegment, respectively. Nodular hyperplasia is the characteristic microscopic change of BPH. It involves cellular hyperplasia plus associated changes in the architecture of the ducts and acini. Nodular hyperplasia in the transition zone is characterized by large amounts of glandular tissue that arise through budding and branching of pre-existing ducts. This latter type of hyperplastic proliferation is a highly unusual finding in adult human tissues, whether normal or diseased. It is felt that this anomalous development results from a reversion of the tissue to more embryonic behaviors.

Pathogenesis

Transition and central zones of the adult prostate gland seem to be of Wolffian duct derivation while the peripheral zone arises from the urogenital sinus (Chapter 6). These diverse embryological origins may explain why BPH occurs within the transition and central zones while prostatic adenocarcinoma originates within the peripheral zone (Fig. 41.1a).

The prostate glandular tissue is unique among the internal genitalia in that it requires dihydrotestosterone (DHT) for normal embryologic development and for maintenance. Testosterone acts as a prohormone. It is converted locally to the more potent androgen DHT by 5α-reductase. DHT potency rests on the higher affinity of the prostatic nuclear androgen receptor for DHT than for testosterone (see Chapter 2).

Differentiation and growth of prostatic epithelium is dependent on androgen-sensitive factors produced in the underlying stroma (embryological mesenchyme). Candidate growth factors increase mitosis in prostatic epithelial cells in vitro and include epidermal growth factor (EGF), insulin-like growth factors (IGFs) and basic fibroblast growth factor (bFGF). Expression of bFGF increases in BPH.

Development of BPH requires a normally functioning testis and 5α-reductase. Individuals lacking 5α-reductase have a vestigial prostate and never develop BPH or prostate cancer. Men with BPH have raised 5α-reductase activity and possibly an increase in prostate androgen receptors, making the “aging” prostate more susceptible to androgen stimulation. There may be a protective role for estrogens in BPH. Estradiol production slowly increases in older men when the testes become less responsive to luteinizing hormone (LH) so that more LH is required to maintain androgen production. High LH levels disproportionately stimulate estrogen production. Elevated circulating estrogens increase hepatic sex hormone-binding globulin (SHBG) synthesis and elevations in SHBG reduce concentrations of free testosterone in the circulation. This decreases the amount of testosterone available to be converted to DHT in the prostatic stroma.

It is believed that the clinical symptoms of BPH are not caused simply by an increase in urethral resistance due to enlargement of the prostate. Many of the symptoms formerly thought to be secondary to BPH are related to age-related bladder dysfunction, generally referred to as lower urinary tract symptoms (LUTS).