Nelson Vergel
Founder, ExcelMale.com
Testosterone Therapy for Menopausal Symptoms
Executive Summary
This document synthesizes findings from a ten-year retrospective study on the use of subcutaneous testosterone pellet therapy for managing menopausal symptoms. The study, conducted at a single gynecologic practice, demonstrates that this therapy provides rapid, sustained, and statistically significant relief for women experiencing androgen deficiency.
The primary outcome, measured by the Menopause Rating Scale (MRS), showed a significant reduction in symptom severity across all 11 categories evaluated (p < 0.0001). Notably, 91% of patients experienced an improvement in their overall MRS scores. Symptom relief was consistent across all patient age groups and peak testosterone levels, suggesting that clinical response, rather than specific age or blood levels, should guide treatment.
While effective, the therapy is associated with manageable side effects. The most common were facial hair and acne, typically addressed by dose reduction or spironolactone. Serious adverse events were infrequent. The study concludes that testosterone pellet therapy is a durable and effective treatment option but calls for further research to establish it as a first-line therapy, optimize dosing, and confirm long-term safety.
1. Background and Context
The management of menopausal symptoms has been a challenging area in medicine, particularly following the 2001 Women’s Health Initiative (WHI) study. The WHI study identified increased risks of breast cancer, dementia, and cardiovascular events with combined estrogen-progestin therapy, leading to a dramatic decrease in its prescription.
Testosterone therapy has emerged as a treatment for androgen deficiency in women, which manifests through a wide range of symptoms:
• Sexual and Genitourinary: Sexual dysfunction, vaginal dryness, urinary complaints.
• Mood and Cognitive: Dysphoric mood, anxiety, irritability, depression, changes in cognition, memory loss.
• Physical: Physical fatigue, insomnia, hot flashes, rheumatoid complaints, loss of energy, muscle weakness.
Despite evidence showing testosterone's effectiveness in improving these symptoms—including those not addressed by estrogen/progesterone alone—most consensus statements do not recommend it for general menopausal management. This reluctance is primarily due to the lack of an FDA-approved product for women and insufficient long-term safety data. The analyzed study aims to evaluate the risks and benefits of subcutaneous testosterone pellet therapy within a community gynecologic practice.
2. Study Design and Methodology
The research was a retrospective review of patients treated with subcutaneous testosterone pellet therapy at a single gynecologic practice between October 2014 and December 2024.
• Patient Cohort: 100 women were identified who received the therapy. Of these, 78 had completed both the initial and follow-up questionnaires required for the analysis.
• Eligibility: Therapy was offered to patients whose menopausal symptoms, particularly those related to androgen deficiency, impacted their daily quality of life.
• Intervention: Patients received subcutaneous testosterone pellets via trocar insertion in the buttock every 12 weeks (+/- 3 weeks). The initial dose was calculated based on ideal body weight (1 mg/pound).
• Outcome Measurement: Symptom severity was quantified using the 11-category Menopause Rating Scale (MRS). Patients completed the MRS questionnaire before their first pellet insertion and again before the third. Symptoms were rated on a scale from 0 (none) to 4 (extremely severe).
• Data Analysis: The study used the non-parametric Wilcoxon signed-rank test for comparing MRS scores and the Bonferroni test to correct for multiple comparisons. A p-value of less than 0.05 was considered statistically significant.
3. Primary Findings: Symptom Improvement
The study found that testosterone pellet therapy resulted in rapid and profound symptomatic relief across the patient population.
3.1. Overall Efficacy
Of the 78 patients with complete data, 71 (91%) showed an improvement in their overall condition. The median total MRS score decreased significantly from a baseline of 17.0 to 7.0 on the follow-up questionnaire (p < 0.0001).
3.2. Symptom-Specific Improvements
Statistically significant improvements were observed in all 11 categories of the MRS. The most dramatic relief was seen in symptoms of sexual problems, vaginal dryness, and depressive mood, where the median score fell to zero.
4. Analysis of Patient Factors
The study analyzed whether patient age or peak testosterone levels correlated with the degree of symptomatic relief.
4.1. Impact of Age
Patients showed significant improvement in MRS scores across all age groups. While the largest improvement was seen in the 50-59 age group, the Spearman correlation found no statistically significant difference in outcomes between the age groups (p = 0.16). This indicates that the therapy is effective for women regardless of age at treatment initiation, from perimenopause into their sixties.
4.2. Impact of Testosterone Levels
Patients were divided into four groups (quartiles) based on their peak testosterone levels. All four groups experienced significant symptomatic relief. A Spearman analysis showed no correlation between peak testosterone levels and the degree of symptom improvement (p = 0.37). This finding supports other studies suggesting that monitoring testosterone levels is unnecessary and that treatment should be based on clinical findings and patient symptoms.
5. Safety Profile and Side Effects
Side effects were reported in 58 of the 100 patients, with 28 reporting more than one. The side effects were generally manageable.
• Most Common Side Effects: The most prevalent issues were facial hair and acne. |
• Management: Side effects were initially treated by reducing the testosterone dose. If symptoms persisted, patients were placed on spironolactone.
• Patient Discontinuation: Four patients discontinued therapy due to persistent side effects. Ten other patients stopped before their sixth dose for geographic relocation.
• Other Adverse Events:
◦ Two women had a hemoglobin level exceeding 15 mg/dl, which was managed with dose reduction.
◦ One patient had elevated liver function tests and was subsequently diagnosed with active hepatitis; therapy was stopped.
◦ Two patients developed breast cancer (one Stage 0, one Stage 1) during the study period. The authors note this number does not seem excessive for the population.
6. Conclusions and Implications
The study provides strong evidence that subcutaneous testosterone pellet therapy is an effective and durable treatment for menopausal symptoms related to androgen deficiency.
• Key Conclusion: The therapy results in rapid, profound, and sustained relief across a wide spectrum of physical, sexual, and psychological symptoms.
• Clinical Implications:
◦ Menopausal symptoms can begin earlier than commonly expected (youngest patient was 38), and treatment should be offered based on desire and quality-of-life impact.
◦ Treatment should be guided by clinical symptom improvement rather than by tracking serum testosterone levels.
◦ Testosterone addresses a broader range of symptoms than topical estrogens alone, making it a compelling treatment option.
• Study Limitations & Future Research: The authors acknowledge the study's limitations, including its observational nature and origin from a single practice. They conclude that while their findings are significant, further studies are necessary to establish efficacy, determine optimal dosing, compare testosterone to other treatments, and evaluate long-term safety before it can be recommended as a first-line therapy for androgen deficiency.
Reference: https://www.sciencedirect.com/science/article/pii/S2590161325000766
Executive Summary
This document synthesizes findings from a ten-year retrospective study on the use of subcutaneous testosterone pellet therapy for managing menopausal symptoms. The study, conducted at a single gynecologic practice, demonstrates that this therapy provides rapid, sustained, and statistically significant relief for women experiencing androgen deficiency.
The primary outcome, measured by the Menopause Rating Scale (MRS), showed a significant reduction in symptom severity across all 11 categories evaluated (p < 0.0001). Notably, 91% of patients experienced an improvement in their overall MRS scores. Symptom relief was consistent across all patient age groups and peak testosterone levels, suggesting that clinical response, rather than specific age or blood levels, should guide treatment.
While effective, the therapy is associated with manageable side effects. The most common were facial hair and acne, typically addressed by dose reduction or spironolactone. Serious adverse events were infrequent. The study concludes that testosterone pellet therapy is a durable and effective treatment option but calls for further research to establish it as a first-line therapy, optimize dosing, and confirm long-term safety.
1. Background and Context
The management of menopausal symptoms has been a challenging area in medicine, particularly following the 2001 Women’s Health Initiative (WHI) study. The WHI study identified increased risks of breast cancer, dementia, and cardiovascular events with combined estrogen-progestin therapy, leading to a dramatic decrease in its prescription.
Testosterone therapy has emerged as a treatment for androgen deficiency in women, which manifests through a wide range of symptoms:
• Sexual and Genitourinary: Sexual dysfunction, vaginal dryness, urinary complaints.
• Mood and Cognitive: Dysphoric mood, anxiety, irritability, depression, changes in cognition, memory loss.
• Physical: Physical fatigue, insomnia, hot flashes, rheumatoid complaints, loss of energy, muscle weakness.
Despite evidence showing testosterone's effectiveness in improving these symptoms—including those not addressed by estrogen/progesterone alone—most consensus statements do not recommend it for general menopausal management. This reluctance is primarily due to the lack of an FDA-approved product for women and insufficient long-term safety data. The analyzed study aims to evaluate the risks and benefits of subcutaneous testosterone pellet therapy within a community gynecologic practice.
2. Study Design and Methodology
The research was a retrospective review of patients treated with subcutaneous testosterone pellet therapy at a single gynecologic practice between October 2014 and December 2024.
• Patient Cohort: 100 women were identified who received the therapy. Of these, 78 had completed both the initial and follow-up questionnaires required for the analysis.
• Eligibility: Therapy was offered to patients whose menopausal symptoms, particularly those related to androgen deficiency, impacted their daily quality of life.
| Inclusion Criteria | Exclusion Criteria |
|---|---|
| Peri-menopausal or menopausal status | Unexplained vaginal bleeding |
| Vaso-motor symptoms | Active breast cancer treatment |
| Androgen deficiency symptoms | History of clotting |
| Persistent/worsening symptoms on oral/topical hormones | Liver dysfunction |
| Cardiovascular risks |
• Intervention: Patients received subcutaneous testosterone pellets via trocar insertion in the buttock every 12 weeks (+/- 3 weeks). The initial dose was calculated based on ideal body weight (1 mg/pound).
• Outcome Measurement: Symptom severity was quantified using the 11-category Menopause Rating Scale (MRS). Patients completed the MRS questionnaire before their first pellet insertion and again before the third. Symptoms were rated on a scale from 0 (none) to 4 (extremely severe).
• Data Analysis: The study used the non-parametric Wilcoxon signed-rank test for comparing MRS scores and the Bonferroni test to correct for multiple comparisons. A p-value of less than 0.05 was considered statistically significant.
3. Primary Findings: Symptom Improvement
The study found that testosterone pellet therapy resulted in rapid and profound symptomatic relief across the patient population.
3.1. Overall Efficacy
Of the 78 patients with complete data, 71 (91%) showed an improvement in their overall condition. The median total MRS score decreased significantly from a baseline of 17.0 to 7.0 on the follow-up questionnaire (p < 0.0001).
3.2. Symptom-Specific Improvements
Statistically significant improvements were observed in all 11 categories of the MRS. The most dramatic relief was seen in symptoms of sexual problems, vaginal dryness, and depressive mood, where the median score fell to zero.
| Symptom Category | Initial MRS Score (Median) | Second MRS Score (Median) | Significance (p-value) |
|---|---|---|---|
| Sexual Problems | 2.5 | 0 | < 0.0001 |
| Depressive Mood | 2 | 0 | < 0.0001 |
| Vaginal Dryness | 2 | 0 | < 0.0001 |
| Physical/Emotional Exhaustion | 2 | 1 | < 0.0001 |
| Hot Flashes / Sweating | 2 | 1 | < 0.0001 |
| Anxiety | 2 | 1 | < 0.0001 |
| Irritability | 2 | 1 | < 0.0001 |
| Sleep Problems | 2 | 1 | < 0.0001 |
| Joint/Muscular Discomfort | 1.5 | 1 | < 0.0002 |
| Heart Discomfort | 1 | 0 | < 0.0001 |
| Bladder Problems | 1 | 0 | < 0.0001 |
4. Analysis of Patient Factors
The study analyzed whether patient age or peak testosterone levels correlated with the degree of symptomatic relief.
4.1. Impact of Age
Patients showed significant improvement in MRS scores across all age groups. While the largest improvement was seen in the 50-59 age group, the Spearman correlation found no statistically significant difference in outcomes between the age groups (p = 0.16). This indicates that the therapy is effective for women regardless of age at treatment initiation, from perimenopause into their sixties.
| Age Group (yrs) | n | Median Improvement (MRS Score) |
|---|---|---|
| < 50 | 21 | 9 |
| 50–59 | 49 | 11 |
| 60–68 | 8 | 5 |
Patients were divided into four groups (quartiles) based on their peak testosterone levels. All four groups experienced significant symptomatic relief. A Spearman analysis showed no correlation between peak testosterone levels and the degree of symptom improvement (p = 0.37). This finding supports other studies suggesting that monitoring testosterone levels is unnecessary and that treatment should be based on clinical findings and patient symptoms.
| Quartile | Testosterone Range (mg/dl) | n | Median Improvement (MRS Score) |
|---|---|---|---|
| 1 | 85.9–115.0 | 20 | 9 |
| 2 | 115.1–137.1 | 19 | 8 |
| 3 | 137.2–189.6 | 19 | 11 |
| 4 | > 189.6 | 20 | 9 |
5. Safety Profile and Side Effects
Side effects were reported in 58 of the 100 patients, with 28 reporting more than one. The side effects were generally manageable.
• Most Common Side Effects: The most prevalent issues were facial hair and acne. |
• Management: Side effects were initially treated by reducing the testosterone dose. If symptoms persisted, patients were placed on spironolactone.
• Patient Discontinuation: Four patients discontinued therapy due to persistent side effects. Ten other patients stopped before their sixth dose for geographic relocation.
• Other Adverse Events:
◦ Two women had a hemoglobin level exceeding 15 mg/dl, which was managed with dose reduction.
◦ One patient had elevated liver function tests and was subsequently diagnosed with active hepatitis; therapy was stopped.
◦ Two patients developed breast cancer (one Stage 0, one Stage 1) during the study period. The authors note this number does not seem excessive for the population.
6. Conclusions and Implications
The study provides strong evidence that subcutaneous testosterone pellet therapy is an effective and durable treatment for menopausal symptoms related to androgen deficiency.
• Key Conclusion: The therapy results in rapid, profound, and sustained relief across a wide spectrum of physical, sexual, and psychological symptoms.
• Clinical Implications:
◦ Menopausal symptoms can begin earlier than commonly expected (youngest patient was 38), and treatment should be offered based on desire and quality-of-life impact.
◦ Treatment should be guided by clinical symptom improvement rather than by tracking serum testosterone levels.
◦ Testosterone addresses a broader range of symptoms than topical estrogens alone, making it a compelling treatment option.
• Study Limitations & Future Research: The authors acknowledge the study's limitations, including its observational nature and origin from a single practice. They conclude that while their findings are significant, further studies are necessary to establish efficacy, determine optimal dosing, compare testosterone to other treatments, and evaluate long-term safety before it can be recommended as a first-line therapy for androgen deficiency.
Reference: https://www.sciencedirect.com/science/article/pii/S2590161325000766
