I know a few of us are watching for the new SARMS on the horizon (orally available non-steroidal nonaromatizable androgen with little impact on the prostate), a number of companies are now tailoring SERMS for TRT.

For example:
Fispemifene is a new, selective estrogen receptor antagonist that is being developed as an oral treatment for testosterone deficiency and associated disorders in men. Symptoms of low testosterone include sexual dysfunction, muscle wasting, reduced bone density, lowered energy levels and glucose intolerance. Unlike testosterone replacement therapies, fispemifene utilizes the body's normal feedback mechanism to increase testosterone levels into, but not beyond, the normal range. By blocking estrogen feedback to the pituitary with a drug like fispemifene, the pituitary increases LH and FSH secretion which increases testosterone secretion. As these rising testosterone levels feedback on the pituitary, LH and FSH secretion return toward normal and testosterone reaches a new, albeit higher, steady state level. Based on this mechanism of action, fispemifene is being studied for the treatment of androgen deficiency and associated symptoms. We believe that increased production of testosterone may treat many of the symptoms of low testosterone. In a Phase II study we conducted in hypogonadal men, fispemifene increased total testosterone levels by 78% over 28 days of treatment.

QuatRx : Fispemifene

Objectives: Clomid (clomiphene citrate) is used to induce ovulation in women. However, Clomid given to men fails to provoke consistently an increase in sperm count.. Most preparations of Clomid contain an unequal mixture of isomers with a predominance of enclomiphene citrate (~60%). We reasoned that the isomer composition and differences in half-life could contribute to the dichotomous affects in men and women.
Design: A randomized, double-blind, placebo-and active-controlled study in hypogonadal men.
Materials and Methods: We evaluated enclomiphene citrate in three doses between 12.5 and 50 mg compared to placebo, and active controls AndroGel® 1% (5.0 G) and Androgel® 1% (10G). Subjects at baseline were low (<250 ng/dL) or borderline low (250 to 350 ng/dL) in total testosterone (TT) with low normal LH and FSH levels. Ten to 11 men completed the study.
Results: After 14 days of oral treatment, the placebo group showed no increase in TT over day 1 but there was a dose-dependent rise with increasing enclomiphene citrate: 12.5 mg per day was associated with a level of 437 + 203 ng/dL; 25 mg per day with 547 + 128 ng/dL, and 50 mg per day with 607 + 184 ng/dL, values in the normal range (298 to 1034 ng/dL). The active-control agent, AndroGel® 1% (5.0 G) resulted in a level 535 + 278 ng/dL and Androgel® 1% (10G) was associated with a level of 608 + 323 . All five treatments were statistically significant compared to Day 1. Levels of free testosterone (FT) by RIA were elevated similarly. Levels of FT as determined by calculation from TT, SHBG, and albumen (performed by Drs. Christina Wang and Ron Swerdloff) were more instructive. All five treatments elevated FT compared to Day 1 and the 25 and 50 mg doses of enclomiphene citrate and the Androgel 1% (10G) treatment were higher than placebo. Androgel® 1% was associated with disproportionate rises in DHT relative to TT (e.g. DHT:TT was 1.59 for the 5G treatment whereas placebo showed a ratio of 1.07 and the 50 mg dose of enclomiphene citrate was associated with a DHT:TT of 0.83)
Conclusions: Enclomiphene citrate (designated as Androxal™) significantly increased total and free testosterone without increasing DHT proportionately. This new agent may represent a new oral modality for elevating testosterone in men with secondary hypogonadism.
Support: None

Looks promising....