Editing Infertility: Management (section)

==== Selective estrogen receptor modulators (SERMs) ====
*'''<span style="color:#ff0000">Mechanism of action: acts as an agonist or antagonist on different estrogen receptors</span>'''
**'''Agonists on receptors in bone, improving bone health'''
**'''<span style="color:#ff0000">Antagonists on receptors on the hypothalamus and pituitary, resulting in increased GnRH</span>'''
***In males, normal binding of estrogen at these receptors functions as an indirect negative feedback mechanism of endogenous testosterone production to down-regulate GnRH and subsequently pituitary gonadotropin production.
*'''<span style="color:#ff0000">Benefits</span>'''
*#'''<span style="color:#ff0000">Increased testosterone'''
*#*<span style="color:#ff0000">'''Treatment with SERMs results in increased GnRH, which then stimulates LH and FSH production by the pituitary gland; the increased LH production, in turn, stimulates Leydig cell production of testosterone'''[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]
*#*Testosterone increase is more than that achieved with anastrazole
*#'''<span style="color:#ff0000">Increased sperm counts</span>'''
*#*See [https://riskcalc.org/clomiphene_citrate/ Risk Calculator] for expected changes for men with infertility who are given clomiphene citrate
*'''<span style="color:#ff0000">Indications</span>'''
**'''Not FDA-approved for use in males'''
***'''<span style="color:#ff0000">Clomiphene citrate is the most commonly used SERM for treating hypogonadism when fertility must be maintained. However, this remains an off-label use.'''
****Enclomiphene citrate, the functional stereoisomer of clomiphene citrate, is currently in commercial development. Its potential advantage is avoidance of the estrogenic side effects of its enantiomer zuclomiphene.
**'''Consider in patients with low testosterone, borderline high/high FSH (lazy pituitary)'''
*Drugs and Dosages
**Examples: clomophene (clomid), tamoxifen
**Available orally
**Clomophene dosing typically starts at 25 mg daily and can be increased up to 100 mg daily.
*'''Adverse events'''
**No specific adverse effects attributed to clomiphene or enclomiphene citrate in males.
**'''Same theoretical risk of testosterone replacement exists'''