Gynecomastia

Introduction

The most common side effects from the use of supplemental estradiol (tE2) in men is gynecomastia (breast growth) and mastalgia (breast/nipple sensitivity). Breast/nipple sensitivity is typically a temporary condition, while breast growth is generally permanent. Concern about breast growth can be a substantial barrier for many men wanting to use tE2 for Androgen Deprivation Therapy (ADT). However, the amount of breast growth that they actually experience may be lower than what they envision.

Do genetic males who take supplemental estrogen develop large breasts?

No. The growth of breast tissue in transgender genetic males (trans women) who take supplemental estrogen (either orally or transdermally), tends to be variable and often minimal. Research indicates that 60-70% of trans women who take supplemental estrogen are dissatisfied with their breast size and subsequently seek out surgical breast augmentation (Alcon et al., 2021; Wierckx et al., 2014).

If I use tE2 for ADT, how much breast development will I experience?
Based on research evidence, it’s likely that your breast growth will be fairly minimal.

In the UK, a large, 14-yr study was conducted to test the effectiveness of transdermal estradiol for treatment of prostate cancer. This study is called the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial. In the PATCH study, 23% of prostate cancer patients who used tE2 for ADT reported no breast growth (Grade 0), 68% reported Grade 1-2 growth, and 19% reported Grade 3 growth (grades are defined below).
Unfortunately, objective measurements of breast volume (or equivalent bra cup size) in men using tE2 for ADT were not made. The only objective measurements of breast growth have been reported for trans women. A majority of trans women in the studies we discuss below had less than an A-cup size, and closer to an AA-cup size, after more than 12 months of estradiol treatment.

Supporting Research

1. de Blok et al. (2018)

  • In this study involving n = 229 trans women (i.e., genetic males) undergoing “Cross-sex Hormone Therapy (CHT),” the average Breast-Chest Difference increased by 3.7 cm after 12 months of treatment.
  • Most of the increase in size occurred within the first 6 months of treatment and then increased at a slower rate from 6-12 months. (See Figure 1). About 84% of the total breast growth occurred within the first 6 months.
  • The degree of breast development did not vary according to age or overall weight change.
  • Almost 50% of trans women had a final breast size equivalent to less than an AAA-cup size (Figure 2).
  • Estrogen patches delivering 50-100 micrograms E2/24hr, changed twice weekly, were used. However, there was no association between serum E2 levels and amount of breast growth.
  • Table 1 summarizes the distribution of equivalent cup sizes after estrogen treatment.,

Figure 1. Average increase in Breast-Chest Difference (in cm) for 229 trans women after 12 months of estradiol treatment (de Blok et al. 2018).

Note: “Breast-Chest Difference” is a measure used to quantify breast size. Breast-Chest Difference is calculated by subtracting the underbust circumference (i.e., where the band of a bra might sit) from the bust circumference (i.e., around the torso at the level of the breasts). See: https://en.wikipedia.org/wiki/Breast_measurement.

Figure 2. Distribution of equivalent bra cup sizes (de Blok et al. 2018).

2. de Blok et al. (2021)

  • In this study of n = 69 trans women, the average Breast-Chest Difference increased by 6 cm after 36 months of hormone treatment (see Figure 3).
  • Estrogen patches delivering 50-150 micrograms E2/24hr, changed twice weekly, were used. However, there was no association between serum E2 levels and amount of breast growth.
  • The final breast volume (as measured by 3D imaging) was about 120 ml, which is equivalent to an A-cup size.
  • The fastest growth occurred during the first 9 months of treatment, but additional growth continued up to 2 years.
  • Table 1 summarizes the distribution of equivalent cup sizes after estrogen treatment.

Figure 3. Changes in Breast Volume and Breast-Chest Difference over 36 months in n = 69 trans women (de Blok et al., 2021).

3. Alcon et al. (2021)

  • This study involved n = 99 trans women who underwent breast augmentation after being on hormone treatment for at least 1 year. This was a retrospective study where the researchers categorized breast development according to a Breast Response to Estrogenic Stimulation in Transwomen (BREST) scale that they developed.
  • A majority (55%) of trans women were categorized as having achieved breast sizes that were less than that would be expected among cisgender females (i.e., genetic females).
  • Findings from this study confirm that a high proportion of trans women were dissatisfied and subsequently seek breast augmentation surgery after undergoing estrogen treatment.

4. Tebbens et al. (2021)

  • In this study of n = 23 trans women taking transdermal or oral estradiol, the median final breast volume was about 94 mL for those using topical E2, and about 87 mL for those using oral E2 (as measured by 3D imaging) after 12 months of treatment. These breast volumes are equivalent to an AA-cup size.
  • Estrogen patches delivering 50-100 micrograms E2/24hr, changed twice weekly, were used. However, there was no association between serum E2 levels and amount of breast growth.

5. Boogers et al. (2024)

  • This study of n = 60 trans women measured breast volume using 3D imaging over a period of 4.5 years.
  • The median final breast volume was 115 ml, which is equivalent to an A-cup size.
  • Estrogen patches delivering 100 micrograms E2/24hr, changed twice weekly, were used. However, there was no association between serum E2 levels and amount of breast growth.

Table 1. Distribution of final breast sizes in trans women using supplemental estrogen.

Reference  nAAA           cup sizeAA            cup sizeA                cup sizeB             cup sizeC              cup size
de Blok (2018)    229      75%14%7%4% 
de Blok (2021)  69  71%9%16%
   Boogers (2021)  60  65%25%10%
       

A weighted average of the final breast equivalent cup sizes was calculated based on the data shown above in Table 1. The study by de Block et al. (2018) had the highest number of trans women (n = 229), so it received the highest weighting factor. The distribution of the weighted averages is shown in Table 2 below. Almost 50% of the final breast sizes of n = 358 trans women after estrogen treatment is equivalent to an AAA-cup size, which represents minimal growth. Figure 4 plots the distribution of cup sizes shown in Table 2.

Table 2. Distribution of weighted average cup sizes after estrogen treatment of n = 358 trans women. [de Blok (2018), de Block (2021), Boogers (2021)].

  Cup Size    Weighted %
    AAA48
      AA9
       A28
       B9
       C6

Figure 4. Distribution of weighted average cup sizes after estrogen treatment of n = 358 trans women. [de Blok (2018), de Block (2021), Boogers (2021)].

Overall, these three studies demonstrate that breast growth was generally minimal in most trans women, even after multiple years of supplemental estrogen exposure.

How do these results for trans women compare to men who used tE2 for ADT?

For the PATCH study, Langley et al. (2013) compared various degrees (grades) of gynecomastia as “adverse events” between standard ADT drugs and tE2 ADT for a total n = 190 men with advanced PCa. These men reported an incidence and severity of gynecomastia caused by ADT. The subjective degree of gynecomastia was divided into four Grade Groups: Grade 0 for no breast growth, Grade 1-2 for “symmetric growth”, and Grade 3 for “asymmetric growth with intervention indicated.” Table 3 summarizes the % of men falling into these four different grade groups, and Figure 5 plots the percentage of 190 men falling into the different grade groups, from the PATCH study.

Table 3. Distribution of gynecomastia Grade Groups for n = 190 men on ADT from the PATCH study. (Langley et al., 2013).

Gynecomastia GradeStandard ADT (n = 78)tE2 ADT  (n = 112)
Grade 081%23%
Grade 1-219%68%
Grade 30%9%

Figure 5. Percentage of n = 190 men on either tE2 ADT or standard ADT that fall into the four gynecomastia Grade Groups. (Langley et al. 2013).

In summary, for men using tE2 for ADT, the incidence of gynecomastia was about 3X more common than for men who used standard ADT. For the tE2 ADT group, 23% of these men reported zero breast growth, 68% reported Grade 1-2 growth (which is equivalent to minimal breast growth), and 9% reported Grade 3 growth (significant, asymmetric breast growth). Surprisingly, 19% of men who used standard ADT drugs also reported having some gynecomastia (despite taking no supplemental estradiol and, thus, having very low estradiol levels).

Unfortunately, the subjective gynecomastiac measurement scale used in the PATCH study (i.e., Grades 0-3) can not be compared to objective measurements of breast volume or an equivalent bra cup size as reported by trans women in the studies summarized above. This makes it difficult, then, to directly compare data from trans women to PCa men using on either tE2 ADT or standard ADT.

Did all groups of study participants receive a similar dose of estrogen from their estradiol patches?

Maybe, yes. It’s important to consider the commercial brand of tE2 patches that were used, and the dose of E2 that may have been ultimately delivered (transdermally) to the bloodstream.

In the studies involving trans women, the average estrogen patch dose that they used was a single patch (changed twice weekly), where each patch delivered an average of 100 micrograms E2/24Hrs (range = 50 to 150 mcg E2/24hrs).

In the PATCH studies of men with PCa, these men used 3-4 “FEM7” patches at a time (changed twice weekly) where each FEM7 patch was also identified as delivering 100 micrograms E2/24hrs.

However, we know (from manufacturer data sheets) that the FEM7 brand of patches generate an average serum E2 level that is only about 1/3 as high as the serum level generated by many other E2 patches that nominally have the same strength (e.g., 100 micrograms E2), such as the Climara™, Alora™, or Vivelle Dot™ brand of patches. So, one could conclude that the serum E2 levels from the E2 patches used in both groups may have been roughly similar.

Summary

Most trans women who took supplemental estradiol experienced minimal breast growth that was equivalent to a bra cup size less than an A-cup, and closer to an AA-cup, even with prolonged exposure to E2 over many years. Most PCa patients who used tE2 for ADT reported Grade 1-2 (68%) or Grade 3 (9%) gynecomastia. Both groups used estradiol patches that may have generated a similar serum E2 level. Breast growth can continue as long as 24 months, while growing at a gradually decreasing rate. Asymmetric gynecomastia, that may warrant “intervention,”, occurs in fewer than 10% of men using tE2 for ADT. For those men, surgery is an option if significant breast tenderness, nipple sensitivity, or psychological distress develops.

References

Alcon A, Wang E, Oliver-Allen H, Srinivasa D, Kim EA. The Breast Response to Estrogenic Stimulation in Transwomen Classification: Evaluation of Breast Response to Estrogenic Stimulation in Transwomen. Ann Plast Surg. 2021 Oct 1;87(4):402-408. doi: 10.1097/SAP.0000000000002729. PMID: 33559998.

Boogers LS, Sardo Infirri SA, Bouchareb A, Dijkman BAM, Helder D, de Blok CJM, Liberton NPTJ, den Heijer M, van Trotsenburg ASP, Dreijerink KMA, Wiepjes CM, Hannema SE. Variations in Volume: Breast Size in Trans Women in Relation to Timing of Testosterone Suppression. J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1404-e1410. doi: 10.1210/clinem/dgae573. PMID: 39150977; PMCID: PMC12012776.

de Blok CJM, Dijkman BAM, Wiepjes CM, Staphorsius AS, Timmermans FW, Smit JM, Dreijerink KMA, den Heijer M. Sustained Breast Development and Breast Anthropometric Changes in 3 Years of Gender-Affirming Hormone Treatment. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e782-e790. doi: 10.1210/clinem/dgaa841. PMID: 33206172.

de Blok CJM, Klaver M, Wiepjes CM, Nota NM, Heijboer AC, Fisher AD, Schreiner T, T’Sjoen G, den Heijer M. Breast Development in Transwomen After 1 Year of Cross-Sex Hormone Therapy: Results of a Prospective Multicenter Study. J Clin Endocrinol Metab. 2018 Feb 1;103(2):532-538. doi: 10.1210/jc.2017-01927. PMID: 29165635.

Langley R, Cafferty FH, Alhasso AA, Rosen SD, Sundaram SK, Freeman SC, Pollock P, Jinks RC, Godland IF, Kockelbergh R, Clarke NW, Kynaston HG, Parmar MBK, Abel PD, Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol 2013; 14:306-316. http://dx.doi.org/10.1016.

Tebbens M, Heijboer AC, T’Sjoen G, Bisschop PH, den Heijer M. The Role of Estrone in Feminizing Hormone Treatment. J Clin Endocrinol Metab. 2022 Jan 18;107(2):e458-e466. doi: 10.1210/clinem/dgab741. PMID: 34632510; PMCID: PMC8764217.