madman
Super Moderator
* Despite effective medical therapy with dopamine agonists and prolactin normalization, over 20 % of men with prolactinomas will remain with hypogonadism.
* There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells.
* Hyperprolactinemia in men causes secondary hypogonadism in 50 % of microprolactinoma and over 70 % of macroprolactinoma patients (Colao et al., 2004).
* Serum prolactin levels are usually 60-200 ng/ml in microprolactinomas, and over 200 ng/ml in most macroprolactinomas.
* Hyperprolactinemic males may suffer from decreased libido, erectile dysfunction, infertility (with low sperm counts), gynecomastia, and rarely galactorrhea.
* Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones.
* Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization
Fig. 1 Mechanisms leading to hypogonadism in male patients with prolactinoma: (A) inhibition of kisspeptin neurons by hyperprolactinemia, and (B) damage to gonadotroph cells secondary to tumor mass effect. GnRH; Gonadotropin Releasing Hormone; KNDy; Kisspeptin, Neurokinin B, and Dynorphin; LH; Luteinising Hormone. Figure created with BioRender.com.
Abstract
Prolactin-secreting adenomas comprise approximately 50 % of all clinically relevant pituitary adenomas. Most men with prolactinomas present with large and invasive tumors. Despite effective medical therapy with dopamine agonists and prolactin normalization, over 20 % of men with prolactinomas will remain with hypogonadism. There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells. Hypogonadism in men results in sexual dysfunction, low libido, anemia, fatigue, and infertility. Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization. For men with prolactinoma and hypogonadism persistence who wish to restore fertility, treatment with gonadotropins or with clomiphene citrate has been found to be safe and effective. In the present review, we propose an algorithm for the management of hypogonadism persistence in men with macroprolactinomas.
2. Mechanisms of hypogonadism in prolactinoma patients
3. Diagnosis
4. Treatment
4.1 Treatment of prolactinomas in men
4.2 Testosterone treatment for men with prolactinoma and hypogonadism
5. Hypogonadism persistence
6. Treatment of hypogonadism and regain of fertility
7. Conclusions
Men with prolactinoma often present with large and invasive tumors. Despite effective drug therapy that usually achieves prolactin normalization, over 20% of men will remain with hypogonadism. The most likely mechanism that causes persistence of central hypogonadism is “tumor mass effect” with destruction of gonadotroph cells in the pituitary gland. Identification of patients who are likely to recover following prolactin normalization is important. Those are men with smaller tumors, higher baseline testosterone levels, without visual defects, and no hypopituitarism. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the HPG axis. However, most men will achieve spontaneous recovery of the gonadal axis within one year after prolactin normalization. For men with prolactinoma and persitent hypogonadism who wish to restore fertility, treatment with gonadotropins or clomiphene citrate may be considered.
* There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells.
* Hyperprolactinemia in men causes secondary hypogonadism in 50 % of microprolactinoma and over 70 % of macroprolactinoma patients (Colao et al., 2004).
* Serum prolactin levels are usually 60-200 ng/ml in microprolactinomas, and over 200 ng/ml in most macroprolactinomas.
* Hyperprolactinemic males may suffer from decreased libido, erectile dysfunction, infertility (with low sperm counts), gynecomastia, and rarely galactorrhea.
* Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones.
* Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization
Fig. 1 Mechanisms leading to hypogonadism in male patients with prolactinoma: (A) inhibition of kisspeptin neurons by hyperprolactinemia, and (B) damage to gonadotroph cells secondary to tumor mass effect. GnRH; Gonadotropin Releasing Hormone; KNDy; Kisspeptin, Neurokinin B, and Dynorphin; LH; Luteinising Hormone. Figure created with BioRender.com.
Abstract
Prolactin-secreting adenomas comprise approximately 50 % of all clinically relevant pituitary adenomas. Most men with prolactinomas present with large and invasive tumors. Despite effective medical therapy with dopamine agonists and prolactin normalization, over 20 % of men with prolactinomas will remain with hypogonadism. There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells. Hypogonadism in men results in sexual dysfunction, low libido, anemia, fatigue, and infertility. Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization. For men with prolactinoma and hypogonadism persistence who wish to restore fertility, treatment with gonadotropins or with clomiphene citrate has been found to be safe and effective. In the present review, we propose an algorithm for the management of hypogonadism persistence in men with macroprolactinomas.
2. Mechanisms of hypogonadism in prolactinoma patients
3. Diagnosis
4. Treatment
4.1 Treatment of prolactinomas in men
4.2 Testosterone treatment for men with prolactinoma and hypogonadism
5. Hypogonadism persistence
6. Treatment of hypogonadism and regain of fertility
7. Conclusions
Men with prolactinoma often present with large and invasive tumors. Despite effective drug therapy that usually achieves prolactin normalization, over 20% of men will remain with hypogonadism. The most likely mechanism that causes persistence of central hypogonadism is “tumor mass effect” with destruction of gonadotroph cells in the pituitary gland. Identification of patients who are likely to recover following prolactin normalization is important. Those are men with smaller tumors, higher baseline testosterone levels, without visual defects, and no hypopituitarism. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the HPG axis. However, most men will achieve spontaneous recovery of the gonadal axis within one year after prolactin normalization. For men with prolactinoma and persitent hypogonadism who wish to restore fertility, treatment with gonadotropins or clomiphene citrate may be considered.
