Adding Kyzatrex (Oral Testosterone) to Clomiphene (Clomid) Improved Symptoms in Non-Responder Men

Abstract​

Introduction
Clomiphene is often used in the treatment of hypogonadal men who wish to preserve endogenous testosterone production, however symptomatic responses are often suboptimal. Exogenous testosterone replacement, while effective, typically suppress the hypothalamic–pituitary-gonadal (HPG) axis. This case series investigates the efficacy of combining clomiphene with high-dose oral testosterone undecanoate (TU) (Kyzatrex, Marius Pharmaceuticals).

Objective
To report the outcomes in a series of patients treated with combined clomiphene and oral TU therapy.

Methods
Three hypogonadal men who initially received clomiphene therapy (50 mg every other day) but did not achieve satisfactory symptomatic improvement despite numerical improvement were identified. Subsequently, they were given oral TU 400 mg once daily with lunch. Subjective symptomatic outcomes, total testosterone (TT), sex hormone binding globulin (SHBG), calculated free testosterone (fT), estradiol, hematocrit (Hct), and HPG axis markers luteinizing hormone (LH) and follicle stimulating hormone (FSH) were monitored at baseline, after 3 months of clomiphene monotherapy, and after 3 additional months of combined clomiphene and oral TU therapy.

Results

The patients had baseline serum testosterone levels of 303, 223, and 230 ng/dL. After 3 months of clomiphene 50 mg QoD, TT rose to 418, 680, and 667 ng/dL respectively, however these patients reported continued symptoms of hypogonadism. After adding 400 mg oral TU once daily for 3 months, TT rose to 1001, 1055, and 1120 ng/dL, and the patients reported significant improvement in symptoms such as erectile dysfunction, fatigue, libido, and exercise tolerance. Both SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU. Hct was unchanged throughout. FSH and LH levels both rose on clomiphene and subsequently dropped after initiation of oral TU, but remained near baseline, indicating preserved HPG axis function. No significant adverse events were reported.

Conclusions
In these patients for whom clomiphene monotherapy failed to generate a sufficient symptomatic response, the addition of high-dose oral TU therapy (Kyzatrex 400 mg) at a once-daily dosing resulted in substantial symptomatic improvement while maintaining endogenous FSH and LH levels at baseline. These findings suggest a novel approach to hypogonadism management, balancing effective symptom relief with preservation of endogenous testosterone production, with potential downstream ramifications on fertility preservation.

https://academic.oup.com/jsm/article/21/Supplement_7/qdae167.201/7919003

 

Abstract​

Introduction
Clomiphene is often used in the treatment of hypogonadal men who wish to preserve endogenous testosterone production, however symptomatic responses are often suboptimal. Exogenous testosterone replacement, while effective, typically suppress the hypothalamic–pituitary-gonadal (HPG) axis. This case series investigates the efficacy of combining clomiphene with high-dose oral testosterone undecanoate (TU) (Kyzatrex, Marius Pharmaceuticals).
Objective
To report the outcomes in a series of patients treated with combined clomiphene and oral TU therapy.
Methods
Three hypogonadal men who initially received clomiphene therapy (50 mg every other day) but did not achieve satisfactory symptomatic improvement despite numerical improvement were identified. Subsequently, they were given oral TU 400 mg once daily with lunch. Subjective symptomatic outcomes, total testosterone (TT), sex hormone binding globulin (SHBG), calculated free testosterone (fT), estradiol, hematocrit (Hct), and HPG axis markers luteinizing hormone (LH) and follicle stimulating hormone (FSH) were monitored at baseline, after 3 months of clomiphene monotherapy, and after 3 additional months of combined clomiphene and oral TU therapy.

View attachment 49402

Results
The patients had baseline serum testosterone levels of 303, 223, and 230 ng/dL. After 3 months of clomiphene 50 mg QoD, TT rose to 418, 680, and 667 ng/dL respectively, however these patients reported continued symptoms of hypogonadism. After adding 400 mg oral TU once daily for 3 months, TT rose to 1001, 1055, and 1120 ng/dL, and the patients reported significant improvement in symptoms such as erectile dysfunction, fatigue, libido, and exercise tolerance. Both SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU. Hct was unchanged throughout. FSH and LH levels both rose on clomiphene and subsequently dropped after initiation of oral TU, but remained near baseline, indicating preserved HPG axis function. No significant adverse events were reported.
Conclusions
In these patients for whom clomiphene monotherapy failed to generate a sufficient symptomatic response, the addition of high-dose oral TU therapy (Kyzatrex 400 mg) at a once-daily dosing resulted in substantial symptomatic improvement while maintaining endogenous FSH and LH levels at baseline. These findings suggest a novel approach to hypogonadism management, balancing effective symptom relief with preservation of endogenous testosterone production, with potential downstream ramifications on fertility preservation.

https://academic.oup.com/jsm/article/21/Supplement_7/qdae167.201/7919003

This is old news now.

Combined Clomiphene and Kyzatrex High-Dose Oral esterified T-Therapy in Hypogonadal Men: A Case Series - Excel Male Health Forum

Hot of the press! You heard it here first! Nelson's domain is where it's at! High-dosed oral TU (Kyzatrex 400 mg) once daily with food + 50 mg clomiphene EOD maintained endogenous LH/FSH near baseline, no change in hematocrit! *Three hypogonadal men who initially received...

www.excelmale.com

 

This is old news now.

Combined Clomiphene and Kyzatrex High-Dose Oral esterified T-Therapy in Hypogonadal Men: A Case Series - Excel Male Health Forum

Hot of the press! You heard it here first! Nelson's domain is where it's at! High-dosed oral TU (Kyzatrex 400 mg) once daily with food + 50 mg clomiphene EOD maintained endogenous LH/FSH near baseline, no change in hematocrit! *Three hypogonadal men who initially received...

www.excelmale.com

Crazy thing to me is that 400 mg in am plus 25 mg clomid at night increased TT more (around 1000 ng/dL) than the 400 BID dosing (looks like TT was around 7-800 in this group). Am I wrong?

 

Wonder if I can do 600 mg in am, and clomid at night, I don’t see any pharmokinetics on 400 bid or 600 once a day…

 

Abstract​

Introduction
Clomiphene is often used in the treatment of hypogonadal men who wish to preserve endogenous testosterone production, however symptomatic responses are often suboptimal. Exogenous testosterone replacement, while effective, typically suppress the hypothalamic–pituitary-gonadal (HPG) axis. This case series investigates the efficacy of combining clomiphene with high-dose oral testosterone undecanoate (TU) (Kyzatrex, Marius Pharmaceuticals).
Objective
To report the outcomes in a series of patients treated with combined clomiphene and oral TU therapy.
Methods
Three hypogonadal men who initially received clomiphene therapy (50 mg every other day) but did not achieve satisfactory symptomatic improvement despite numerical improvement were identified. Subsequently, they were given oral TU 400 mg once daily with lunch. Subjective symptomatic outcomes, total testosterone (TT), sex hormone binding globulin (SHBG), calculated free testosterone (fT), estradiol, hematocrit (Hct), and HPG axis markers luteinizing hormone (LH) and follicle stimulating hormone (FSH) were monitored at baseline, after 3 months of clomiphene monotherapy, and after 3 additional months of combined clomiphene and oral TU therapy.

View attachment 49402

Results
The patients had baseline serum testosterone levels of 303, 223, and 230 ng/dL. After 3 months of clomiphene 50 mg QoD, TT rose to 418, 680, and 667 ng/dL respectively, however these patients reported continued symptoms of hypogonadism. After adding 400 mg oral TU once daily for 3 months, TT rose to 1001, 1055, and 1120 ng/dL, and the patients reported significant improvement in symptoms such as erectile dysfunction, fatigue, libido, and exercise tolerance. Both SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU. Hct was unchanged throughout. FSH and LH levels both rose on clomiphene and subsequently dropped after initiation of oral TU, but remained near baseline, indicating preserved HPG axis function. No significant adverse events were reported.
Conclusions
In these patients for whom clomiphene monotherapy failed to generate a sufficient symptomatic response, the addition of high-dose oral TU therapy (Kyzatrex 400 mg) at a once-daily dosing resulted in substantial symptomatic improvement while maintaining endogenous FSH and LH levels at baseline. These findings suggest a novel approach to hypogonadism management, balancing effective symptom relief with preservation of endogenous testosterone production, with potential downstream ramifications on fertility preservation.

https://academic.oup.com/jsm/article/21/Supplement_7/qdae167.201/7919003

Very interesting study Nelson. Thank you for sharing. Any thoughts on what the equivalent protocol would be using enclomiphene vs clomiphene? Thank you!

 

Very interesting study Nelson. Thank you for sharing. Any thoughts on what the equivalent protocol would be using enclomiphene vs clomiphene? Thank you!

I don't think anything related to dose would change.

 

I don't think anything related to dose would change.

Thank you Nelson. I'm thinking of trying this protocol but might use 25mg enclomiphene EOD vs the 50mg clomiphene EOD.

 

Thank you Nelson. I'm thinking of trying this protocol but might use 25mg enclomiphene EOD vs the 50mg clomiphene EOD.

I’m doing 400 mg kyzatrex at 7 am, 200 mg at noon and 200 mg at 1 pm (to lessen the peaks), 12.5 enclomiphene at 7 pm… if you plot out TT, it’ll be 7-800 until around 5pm then drops to around 300 at night which should allow the enclomiphene to work:

 

I’m doing 400 mg kyzatrex at 7 am, 200 mg at noon and 200 mg at 1 pm (to lessen the peaks), 12.5 enclomiphene at 7 pm… if you plot out TT, it’ll be 7-800 until around 5pm then drops to around 300 at night which should allow the enclomiphene to work:

How did this work out? I am also thinking of doing this?

 

I’m doing 400 mg kyzatrex at 7 am, 200 mg at noon and 200 mg at 1 pm (to lessen the peaks), 12.5 enclomiphene at 7 pm… if you plot out TT, it’ll be 7-800 until around 5pm then drops to around 300 at night which should allow the enclomiphene to work:

Did it work out well for you?

 

Did it work out well for you?

Not good. I developed intense brain fog and fatigue, to the point it was unbearable. I felt like utter crap. I’m back on 50 mg test cyp twice a week and feel great.

 

Not good. I developed intense brain fog and fatigue, to the point it was unbearable. I felt like utter crap. I’m back on 50 mg test cyp twice a week and feel great.

Darn, I was hoping it worked out. Do you know if it worked out for anyone? I am concerned about hair loss and atrophy, so injections will be my last resort. My plan was to continue enclo and occasionally take kyzatrex, ,maybe once in the afternoon.

 

Darn, I was hoping it worked out. Do you know if it worked out for anyone? I am concerned about hair loss and atrophy, so injections will be my last resort. My plan was to continue enclo and occasionally take kyzatrex, ,maybe once in the afternoon.

I was too far gone, 10 years into trt, I bet if just starting it may work. There was a study that showed it worked but it was a N of 3

 

I was too far gone, 10 years into trt, I bet if just starting it may work. There was a study that showed it worked but it was a N of 3

Newer data N = 20!

Baseline ---> CC 50 mg QOD x 3 mo ---> CC + oral TU 400 mg QD x 3mo


* 18/20 (90%) reported SIGNIFICANT SYMPTOM IMPROVEMENT

* 3 spontaneous natural conceptions

* No testicuoar atrophy observed

* 2 mild AEs (nausea, headache)

* 2 developed Hct >52% ---> resolved with dose reduction

Thread 'A Novel Combination Therapy for Testosterone Deficiency: Clomiphene Citrate With Oral TU Provides Symptomatic Relief With HPGA Preservation'

Dec 4, 2025

https://academic.oup.com/jsm/article/22/Supplement_4/qdaf320.053/8375197

A Novel Combination Therapy for Testosterone Deficiency: Clomiphene Citrate With Oral Testosterone Undecanoate Provides Symptomatic Relief With Hypothalamic-Pituitary-Gonadal Axis Preservation

A video from Andrew Sun, posted on Dec 3, 2025.

www.vumedi.com

• madman
• hypogonadism; fertility; clomid/oral tu; hpga
• Replies: 5
• Forum: hCG, Clomid & Others for Fertility, PCT or Low T

• 

Post in thread 'New Breakthrough for Low T: Combining Clomiphene Citrate with Oral TU (Kyzatrex) Boosts T Levels, Preserves Fertility, and Improves Symptoms'

Dec 5, 2025

Nice data to look at, but only 3 random men in a busy urology practice is not exactly robust data. It may be right, however, since the data do make sense.

Did you miss this?

* Larger prospective trials warranted




post # 1/5

Twenty men.

A Novel combination Therapy for Testosterone Deficiency: Clomiphene Citrate with Oral testosterone Undecanoate Provides Symptomatic Relief With Hypothalamic Pituitary-Gonadal Axis Preservation (2025)

Methods

This retrospective chart review included 20 men, aged 23-72 years, from a high-volume...

• madman