Estradiol for Polycystic Ovary Syndrome

(CRM009 Trial)

Overseen By Christopher McCartney, M.D.

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Virginia

Disqualifiers: Males, Pregnancy, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to determine if estradiol augmentation of luteinizing hormone (LH) secretion secretion (primary endpoint) and follicle-stimulating hormone (FSH) secretion (secondary endpoint) is reduced in adult women with polycystic ovary syndrome.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should be in general good health, except for certain conditions like PCOS and adequately-treated hypothyroidism, which suggests that some medications might be allowed.

Is estradiol safe for treating polycystic ovary syndrome?

The research does not provide specific safety data for estradiol in treating polycystic ovary syndrome, but a study on a similar hormone treatment (desogestrel and ethinylestradiol) showed only moderate changes in lipid levels, suggesting it may be generally safe. However, more specific studies on estradiol are needed to confirm its safety. ^{1 2 3 4 5}

How does the drug Estradiol differ from other treatments for polycystic ovary syndrome?

Estradiol is unique because it is a form of estrogen that can help balance hormone levels in women with polycystic ovary syndrome (PCOS), potentially improving symptoms like irregular periods and excess hair growth. Unlike some other treatments that focus on inducing ovulation or reducing androgens, Estradiol primarily works by supplementing estrogen levels, which may help regulate the menstrual cycle and improve overall hormonal balance. ^{1 6 7 8 9}

What data supports the effectiveness of the drug Estradiol for treating polycystic ovary syndrome?

One study suggests that maintaining a certain level of estradiol (a form of estrogen) in the blood can help induce ovulation in women with polycystic ovaries, which is a key concern in polycystic ovary syndrome. ^{1 6 8 10 11}

Who Is on the Research Team?

Christopher M McCartney, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adult women aged 18-30 with Polycystic Ovary Syndrome (PCOS), characterized by excess male hormones and irregular periods, but no other health issues. Participants must avoid pregnancy and have regular menstrual cycles if they're in the control group without PCOS signs.

Inclusion Criteria

I am able and willing to agree to the study's procedures and risks.

I am a woman aged 18-30 with PCOS, showing signs of high male hormones and irregular periods.

I am a woman aged 18-30, have regular periods, and show no signs of excessive male hormones.

Exclusion Criteria

I am a female.

I am over 30 years old.

My hormone levels suggest I might have a specific adrenal gland condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Estradiol Administration

Participants receive transdermal estradiol patches applied daily to maintain serum estradiol levels of 250-400 pg/ml

7-9 days

Daily visits for patch application and monitoring

Monitoring and Data Collection

Daily blood draws and urine collection for hormone measurements; transvaginal ultrasound on study day 6

7-9 days

Daily visits for blood draws and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol

Trial Overview The study tests whether estradiol, a form of estrogen, affects the secretion of hormones involved in ovulation differently in women with PCOS compared to healthy controls. It measures luteinizing hormone as its main focus and follicle-stimulating hormone secondarily.

How Is the Trial Designed?

Group I: Transdermal Estradiol Experimental Treatment 1 Intervention

Subjects will undergo estradiol administration for up to 9 days. Transdermal estradiol patches will be applied each day by study staff during study days two through nine (patches deliver 0.1 mg/day for a total dose of up to 0.6 mg/day).

Estradiol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

The combination pill of ethinyl estradiol (EE) and desogestrel (DSG) significantly improved hyperandrogenic symptoms, such as reduced Ferriman-Gallwey scores and lower serum testosterone levels, in women with polycystic ovary syndrome (PCOS) during the first 6 months of treatment.

However, after 12 months, no further improvements were observed, and the treatment did not adversely affect insulin sensitivity or body weight, indicating that while effective initially, the benefits may plateau over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ethinyl estradiol and desogestrel on clinical and metabolic parameters in Indian patients with polycystic ovary syndrome. Bhattacharya, SM., Ghosh, M., Basu, R.[2013]

Letrozole is as effective as human menopausal gonadotropin (HMG) in inducing ovulation and achieving pregnancy in patients with polycystic ovary syndrome (PCOS) who are resistant to clomiphene citrate, with similar ovulation rates (53.6% for letrozole vs 64.7% for HMG).

Letrozole has a lower incidence of ovarian hyperstimulation syndrome (2 cases) compared to HMG (12.5% incidence), making it a safer option for inducing ovulation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resistance polycystic ovary syndrome patients: A randomized controlled study. Shi, S., Hong, T., Jiang, F., et al.[2022]

In a study of 80 infertile women with polycystic ovarian syndrome, letrozole was found to improve endometrial thickness compared to clomiphene citrate, suggesting better conditions for implantation.

While clomiphene citrate resulted in higher levels of dominant follicles and oestradiol, letrozole showed lower resistance and pulsatility indices, indicating a potentially more favorable environment for pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with polycystic ovarian syndrome. Al-Obaidi, MT., Ali, ZH., Al-Saadi, WI., et al.[2022]

Letrozole significantly outperformed clomiphene citrate in inducing ovulation, with a risk ratio of 1.14, and also showed higher rates of clinical pregnancies (RR 1.48) and live births (RR 1.49) in a systematic review of 29 randomized controlled trials involving 3,952 women with PCOS.

The study suggests that letrozole is a more effective option for ovulation induction in women with infertility and PCOS compared to clomiphene citrate, although the overall quality of the evidence was mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole Compared With Clomiphene Citrate for Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis. Liu, Z., Geng, Y., Huang, Y., et al.[2023]

In a study of 18 women with polycystic ovaries, it was found that an estradiol/testosterone ratio of 0.09 or higher significantly improved the chances of inducing ovulation when using Clomiphene Citrate.

The research suggests that maintaining a baseline estrogen plasma concentration of 50 pg/ml may be important for achieving the desired antiestrogenic effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The polycystic ovary. I. Estradiol/testosterone ratio and the use of antiestrogens. Cortés-Gallegos, V., Legarreta, ME., Aranda, IS., et al.[2013]

In a study of 92 women with Polycystic Ovarian Syndrome (PCOS), the Letrozole stair-step protocol achieved an ovulation rate of 96%, which is comparable to the 88% ovulation rate seen with Clomiphene Citrate (CC), indicating both treatments are effective for ovulation induction.

Letrozole resulted in a shorter time to ovulation (19.5 days) compared to CC (23.1 days), suggesting it may be a more efficient option for women seeking to conceive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovulation rates in a stair-step protocol with Letrozole vs clomiphene citrate in patients with polycystic ovarian syndrome. Thomas, S., Woo, I., Ho, J., et al.[2022]

In a study of 100 women with PCOS, letrozole showed a higher ovulation rate (86.0%) compared to clomiphene citrate (72.0%), although this difference was not statistically significant.

Letrozole also resulted in a significantly shorter time to ovulation (17.20 days) compared to clomiphene citrate (24.08 days), while both treatments had similar safety profiles regarding side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing efficacy and safety of stair step protocols for clomiphene citrate and letrozole in ovulation induction for women with polycystic ovary syndrome (PCOS): a randomized controlled clinical trial. Al-Thuwaynee, S., Swadi, AAJ.[2023]

Letrozole is as effective as clomiphene citrate for inducing ovulation in women with PCOS, with both treatments achieving follicle maturation in similar time frames.

However, letrozole resulted in a significantly thicker endometrial lining and a higher pregnancy rate after intrauterine insemination, while producing fewer follicles, which may reduce the risk of multiple pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination. Hendawy, SF., Samaha, HE., Elkholy, MF.[2021]

In a study of 20 women with polycystic ovary syndrome (PCO) treated with desogestrel and ethinylestradiol for 3 months, 70% experienced weight loss, but there were only moderate changes in lipid levels, including increased triglycerides and cholesterol.

The treatment did not significantly improve lipid profiles compared to healthy controls, indicating that while it may help with weight management, it does not provide additional benefits for lipid health in women with PCO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid metabolic studies in women with a polycystic ovary syndrome during treatment with a low-dose desogestrel-ethinylestradiol combination. Cullberg, G., Hamberger, L., Mattsson, LA., et al.[2019]

In a study of 32 women with polycystic ovary syndrome (PCOS), those treated with ethinyloestradiol and cyproterone acetate (EO-CA) for 6 months experienced significant reductions in hirsutism and serum androgen levels, but also showed decreased insulin sensitivity.

Conversely, women treated with the GnRH analogue goserelin had decreased androgen levels and improved insulin sensitivity, although they did not see a significant reduction in hirsutism, indicating different mechanisms of action between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome. Dahlgren, E., Landin, K., Krotkiewski, M., et al.[2019]

The low estrogen-containing oral contraceptive Loestrin effectively normalized hormone levels in 25 women with polycystic ovary disease, reducing elevated luteinizing hormone and testosterone levels while increasing testosterone binding globulin.

Treatment with Loestrin led to noticeable improvements in symptoms, such as reduced hair growth and better complexion, within 12 to 16 weeks, with minimal side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normalization of testosterone levels using a low estrogen-containing oral contraceptive in women with polycystic ovary syndrome. Raj, SG., Raj, MH., Talbert, LM., et al.[2019]

Citations

1. Australia pubmed.ncbi.nlm.nih.gov

Effects of ethinyl estradiol and desogestrel on clinical and metabolic parameters in Indian patients with polycystic ovary syndrome. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resistance polycystic ovary syndrome patients: A randomized controlled study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with polycystic ovarian syndrome. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Letrozole Compared With Clomiphene Citrate for Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The polycystic ovary. I. Estradiol/testosterone ratio and the use of antiestrogens. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Ovulation rates in a stair-step protocol with Letrozole vs clomiphene citrate in patients with polycystic ovarian syndrome. [2022]

7. Romania pubmed.ncbi.nlm.nih.gov

Comparing efficacy and safety of stair step protocols for clomiphene citrate and letrozole in ovulation induction for women with polycystic ovary syndrome (PCOS): a randomized controlled clinical trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Lipid metabolic studies in women with a polycystic ovary syndrome during treatment with a low-dose desogestrel-ethinylestradiol combination. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Normalization of testosterone levels using a low estrogen-containing oral contraceptive in women with polycystic ovary syndrome. [2019]