Side effects from Letrozole I have been taking since June 2022.
1. Joint/muscle aches: CoQ10: Ubiquinal 100mg daily
2. Hot Flashes: Estroven Complete (Rhubarb Extract) NO Estrogen. Daily
3. Vaginal Dryness: Revaree Vaginal Suppositories
4. Vaginal Dryness: Coconut Oil
5. Eye Dryness: Eye Drops- Generic
6. Vaginal Atrophy, dryness, Urinary Incontinence: Imvexxy 10mg or 4mg Vag. Suppository. This is ESTROGEN however, approved by my Medical Oncologist.
ALL of the above have GREATLY IMPROVED the side effects I was experiencing from the Aromatase Inhibitor drugs I was on Anastrozole prior to Letrozole which was HORRIBLE.
Feel free to reach out and ask me questions if you would like. Thanks!

I think the problem starts with pharmaceutical studies to determine the maximum tolerable dose, rather than the minimum effective dose. We all end up overtreated!

Before Letrozole my lipid profile was good enough that I didn't need any statin. When my primary care doctor ordered that profile this year, my cholesterol was an off the charts 413 thanks to Letrozole!
This is a side effect you can't feel and one my oncologist never mentioned or monitored. Unfortunately it looks like the lower dose doesn't help here either.

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From the study protocol, here is the reason why the PIs chose exemestane over other AIs. I read through the full protocol before deciding to present my case to my medical oncologist

Exemestane is in fact a steroidal aromatase inactivator with a long-lasting effect attributable to a tight covalent binding to the enzyme. The estradiol suppression persists for at least 5 days after administration of a single dose (10). This suggests, especially in a prevention setting, the possibility to reduce the dose and change the time schedule, while still maintaining a significant estradiol reduction. A study of 10 patients found that women who took a daily dose of 10 mg of exemestane achieved equivalent estradiol suppression as women who took a dose of 25 mg daily (11).
The exemestane steroidal structure suggests it may have androgenic properties that could potentially counteract any anti-estrogenic properties in bone and possibly sexual function and menopausal symptoms.
The favorable profile on bone may represent an advantage of this agent in prevention settings in unaffected women at increased risk for breast cancer.

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@A MyBCTeam Member @A MyBCTeam Member

Here from ASCO post

In a phase IIb trial reported in JAMA Oncology, Serrano et al found that exemestane at 25 mg three times weekly was noninferior to the standard dosing of 25 mg once daily in terms of serum estradiol reduction among postmenopausal patients with stage 0 to II estrogen receptor (ER)-positive breast cancer who were compliant with study regimens.

In the international, multicenter, double-blind trial, 171 evaluable patients who were candidates for surgery were randomly assigned 1:1:1 between February 2017 and August 2019 to receive exemestane at 25 mg three times weekly (n = 56), once weekly (n = 60), or once daily (n = 55) for 4 to 6 weeks prior to surgery. The primary outcome measure was percentage change in serum estradiol level determined by solid-phase extraction from baseline to final visit prior to surgery, with a noninferiority margin of –6% for the two lower-dose regimens vs the standard regimen.

Key Findings

The least square mean percentage change in serum estradiol was −89% in the once-daily group, −85% in the three-times-weekly group, and −60% in the once-weekly group. The difference in estradiol percentage change between the once-daily group and the three-times-weekly group was −3.6% (P for noninferiority = .37).

Compliance was defined as taking ≥ 80% of prescribed pills. Among 153 compliant patients, the least square mean percentage change in estradiol was −91% in the once-daily group, −92% in the three-times-weekly group, and −69% in the once-weekly group. The difference in estradiol percentage change between the once-daily group and the three-times-weekly group was +2.0% (97.5% lower confidence limit = −5.6%, P for noninferiority = .02). No significant differences in adverse events were observed among patients across the three groups.

The investigators concluded, “In this randomized clinical trial, exemestane [at] 25 mg given three times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in [patients] who do not tolerate the daily dose in the adjuvant setting.”

Andrea DeCensi, MD, of Ospedali Galliera, Genova, Italy, is the corresponding author for the JAMA Oncology article.

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I have tried to stop all treatment and let nature take it's course. I am 82 years old and do not have a life anymore. I live alone, my husband passed nearly 6 years ago. I do not drive anymore so I need to have a driver everywhere I go. My daughter is this person, but we need to make my appointments to fit her schedule. Not easy! My oncologist just keeps coming up with a new way every time I see her. How do I convince her I want to stop?