High E2 (~50 pg/mL) on HCG/Enclomiphene/Anastrozole: Mood, Acne, Fog

[Tankeryanker123]

I'm 38, on a fertility protocol/hormone optimization (HCG 250 IU 2x/week, Enclomiphene 12.5 mg daily, Anastrozole) for 80 days. Latest blood work (May 16th 2025): T level at 1376 ng/dL, E2 at 50-55 pg/mL.

Doc said E2 was high, so they increased Anastrozole to 0.25 mg 2x/week ~2 weeks ago. Still having symptoms: low/sad mood, back/shoulder/chest acne, brain fog, some anxiety. The symptoms are somewhat mild but definitely present and noticeable. The acne symptom is heavy though. Is this normal?

I drink ~2-3 drinks (beers/shots) on 2-3 off days/week, which might be keeping E2 high Planning to cut alcohol and discuss with doc soon. Tips for managing mood, acne, fog, or lowering E2?

 

[WhiteMale]

Keep treating symptoms, those are all key E symptoms.

Body acne was a massive problem for me when my E was too high, for me, vs. what a blood test would show. In a vacuum, treat your symptoms.

Reduce enclomiphene dose or frequency, your HCG dose is miniscule as it is. Just throwing that out there. Too I doubt your alcohol intake is the root or key player.

 

[chriskchris]

Not sure I've ever seen someone on HCG and Clomid at the same time. That is a odd mix.

When I took Clomid years ago, my testosterone was high but E2 went off the charts. It was a test project to see if I was primary or secondary, I felt amazing at first and then worst then ever. The doctor at the time suggested I then take 1mg of Arimidex per day which made me feel like walking dead. I think I would have died had I contind taking his advice. Saved my the knowledge of the forums as some docs as good hearted as they are have no clue about TRT as they don't often treat it in depth.

Anastrozole can cause me nasty side effects. Not sure if it is from the drug itself or crashing E2, something I have done numerous times even in small doses. I get horrendous veritgo, achy joints, dizziness, poor penile sensation, difficulty to sleep despite fatigue and some of the worst headaches of my life.

I think it's the E2 low (crash) that does it rather then anastrozole. If I took .50 mg of anastrozole it would drive me to nearly zero even on HCG. If I take .125 of anastrozole I find my nocturnal erections come back and the 'bloating' and other high e2 symptoms go away. I can manage 1-2x dose of .125 per week on 100mg of cypionate and 300 miu x 3 of HCG. E2 can go as high as 80 on that regiment, but will fall into the 10-20 pg/ml range on as little as .125 mg of anstrozole.

I believe the consensus is that it is very hard to manage E2 on Clomid regardless because of the aromatization process.

Biggest thing I learned is that it is better only to take anastrozole when you feel the high e2 symptoms rather then take it systematically as the anastrozole is so powerful, it can crash your estradiol easily even in small amounts which is the worst feeling of all feelings from my experience.

All the best.

 

[Tankeryanker123]

Very good info. Thank youguys alot. Yeah after the increase of Anastrozole to 0.25mg twice weekly it has brought down my E2 to 31. Blood work after one month showed T at 1277 and E2 at 31. I must say the bloating has stopped and acne has improved, no more crying as well. But the personality social energy feels flat. Brainfog still present. Seems like erections are working but not much drive to initiate. I like the idea that @chriskchris suggested about only taking the Anastrozole with symptoms to figure out what's the best e2 levels for me as it varies for people. Figured my e2 might be best at a little higher levels. Definitely will talk to doc about it. Thanks for all the info.

 

[FunkOdyssey]

I'm 38, on a fertility protocol/hormone optimization (HCG 250 IU 2x/week, Enclomiphene 12.5 mg daily, Anastrozole) for 80 days. Latest blood work (May 16th 2025): T level at 1376 ng/dL, E2 at 50-55 pg/mL.

Doc said E2 was high, so they increased Anastrozole to 0.25 mg 2x/week ~2 weeks ago. Still having symptoms: low/sad mood, back/shoulder/chest acne, brain fog, some anxiety. The symptoms are somewhat mild but definitely present and noticeable. The acne symptom is heavy though. Is this normal?

I drink ~2-3 drinks (beers/shots) on 2-3 off days/week, which might be keeping E2 high Planning to cut alcohol and discuss with doc soon. Tips for managing mood, acne, fog, or lowering E2?

You're taking too much of everything. You don't need to be at 1376 ng/dL to get someone pregnant. I bet you could get the job done fertility-wise with a lower dose of enclomiphene like 6.25 mg, no hCG, no AI, and feel a hell of a lot better than you do now.

 

[Tankeryanker123]

You're taking too much of everything. You don't need to be at 1376 ng/dL to get someone pregnant. I bet you could get the job done fertility-wise with a lower dose of enclomiphene like 6.25 mg, no hCG, no AI, and feel a hell of a lot better than you do now.

Thanks! A giant thing I forgot to mention is I'm not actually trying to conceive until next year atleast. I only got on this protocol because I was told TRT would destroy fertility permanently during the consultation. I don't have any kids yet so I told the clinic that I would opt out of direct test for now (they initially perscribed a small dose of it). Me expressing fertility concerns is the reason why they switched it to this protocol. They told me this would optimize my levels without killing fertility, but i also wont be reaching the great levels i would get with trt, which was fine with me. With that in mind, would you suggest still dropping the hcg or and lowering Enclomiphene? Or just dropping the entire protocol all together until im ready to go full in with trt?

 

[FunkOdyssey]

Thanks! A giant thing I forgot to mention is I'm not actually trying to conceive until next year atleast. I only got on this protocol because I was told TRT would destroy fertility permanently during the consultation. I don't have any kids yet so I told the clinic that I would opt out of direct test for now (they initially perscribed a small dose of it). Me expressing fertility concerns is the reason why they switched it to this protocol. They told me this would optimize my levels without killing fertility, but i also wont be reaching the great levels i would get with trt, which was fine with me. With that in mind, would you suggest still dropping the hcg or and lowering Enclomiphene? Or just dropping the entire protocol all together until im ready to go full in with trt?

What were your starting levels and symptoms that led you to a hormone optimization clinic? You haven't mentioned free T yet, and that needs to be talked about (your original baseline and what it is currently), as that is far more important than your total testosterone. It can be calculated from SHBG if you have those levels.

Assuming all you want to do is enjoy a testosterone boost without compromising your fertility, yes, a lower dose of enclomiphene without either hCG or the AI would make alot more sense.

 

[Tankeryanker123]

What were your starting levels and symptoms that led you to a hormone optimization clinic? You haven't mentioned free T yet, and that needs to be talked about (your original baseline and what it is currently), as that is far more important than your total testosterone. It can be calculated from SHBG if you have those levels.

Assuming all you want to do is enjoy a testosterone boost without compromising your fertility, yes, a lower dose of enclomiphene without either hCG or the AI would make alot more sense.

So for the starting levels my T was at 654, E2 was at 39.7, SHBG at 33 and Free -T was at 13.5. Mostly within normal ranges i assume. What led me to the clinic is I was gaining weight that I couldn't shake and struggling with libido, mainly due to brutal work schedule. 65 average hours per week with the shift of 3pm to 3am, sometimes later. Moderate physical labor. Felt motivation slipping so I decided I should inquire about trt, then came across this protocol.

Started March 6. As of now I've lost 20-24 pounds. Much leaner. Definitely stronger in the gym, though not the beast mode it would be on trt (I'm fine with that). So it feels like if I can just get a little bit of things tweaked, for better mood and mental clarity, I'll be great. I can say there were a couple of short, quick periods of time where I felt great in all aspects, when the levels were first adjusting up and down. Looking for that sweet spot.

Yeah, you hit the nail on the head with the goal. Basically enjoy a T boost without compromising fertility. After having a kid or 2 I'll be more open to T replacement.

 

[FunkOdyssey]

So for the starting levels my T was at 654, E2 was at 39.7, SHBG at 33 and Free -T was at 13.5. Mostly within normal ranges i assume.

Yes, this was all very normal. E2 was probably on the high side because of the extra fat you hadn't lost yet.

What led me to the clinic is I was gaining weight that I couldn't shake and struggling with libido, mainly due to brutal work schedule. 65 average hours per week with the shift of 3pm to 3am, sometimes later. Moderate physical labor. Felt motivation slipping so I decided I should inquire about trt, then came across this protocol.

You seem to correctly understand that the cause of your symptoms was probably stress, and not testosterone deficiency. There are different schools of thought around TRT and testosterone therapy more broadly: some believe it should be available to any adult male that wants to optimize their levels for any reason (I'm in this camp), others believe it should be reserved for only legitimate cases of hypogonadism. And then, how you define legitimate hypogonadism is another debate, but there is no definition I'm aware of that would include you.

So it feels like if I can just get a little bit of things tweaked, for better mood and mental clarity, I'll be great. I can say there were a couple of short, quick periods of time where I felt great in all aspects, when the levels were first adjusting up and down. Looking for that sweet spot.

Yeah, you hit the nail on the head with the goal. Basically enjoy a T boost without compromising fertility. After having a kid or 2 I'll be more open to T replacement.

My strong non-medical advice opinion: the correct thing to do here is enclomiphene alone. Play with dosage (6.25 mg vs 3.125 mg), play with frequency (daily vs EOD). A little goes a long way, too much will start backfiring in areas like mood and libido. hCG is adding nothing but side effects here. AI often harms mood, libido and overall health.