Following known articles for induction of lactation [6,7,8,9,10,11], the patient was initially treated with 6 mg estradiol and 10 mg domperidone. There are no guidelines for induced lactation in transgender women, so we increased the hormone dosage based on periodic blood tests and patient symptoms. At the time of the treatment of the current patient, there had only been two previous transgender breastfeeding papers [6, 7]. Therefore, although estradiol, progesterone, and prolactin were monitored with reference values, it was difficult to evaluate the test results. Because of concerns regarding leg vein thrombosis associated with high-dose estrogen, and arrhythmia and dyskinesia associated with high-dose domperidone, the lower extremities were carefully visually inspected and examined neurologically, and ECG was regularly monitored. Blood tests were performed as an adjunct to screen for thrombosis by measuring D-dimer.

On day 39 of treatment, 100 mg progesterone was started, and on day 46, nipple stimulation (four times/day) with a breast pump was started along with 6 mg estrogen, 100 mg progesterone, and 30 mg domperidone. A midwife provided in-person and online guidance on how to promote lactation. On day 53, progesterone was increased to 200 mg, and on day 59, progesterone (300 mg) and domperidone (60 mg) were increased, and estradiol (6 mg) was continued. On day 63, in addition to 6 mg estradiol, 1 mg estradiol gel was added with 500 mg progesterone and 60 mg domperidone, and lactation was observed on the same day. After lactation was confirmed, the frequency of pumping was increased from four to six times/day, and on day 99, the total estrogen dose was increased to 8 mg (6 mg oral + 2 mg gel). Transdermal estrogen administration was added to bring the estrogen concentration closer to that of the gestational age. Considering age and other factors, the risk of estradiol-induced venous thromboembolism was considered high, and transdermal rather than oral agents were chosen for estrogen administration, as recommended in the guidelines [12]. The initial milk production was only a few drops. Subsequently, 8 mg estradiol, 500 mg progesterone, and 80 mg domperidone were administered to continue pseudo-gestation. We did not increase estrogen and progesterone levels to gestational and postpartum levels because of the risk of venous thromboembolism, and because milk production was observed, the levels of estrogen and progesterone were simply maintained. According to reference literature on induced breast milk [13], the maximum dosage of domperidone was 80 mg/day. Therefore, initial treatment was domperidone at 10 mg/day, with the dosage increased according to the patient’s physical condition. One paper on induced breast milk in transgender women reported prolactin levels above 100 ng/mL [6], so we adjusted the domperidone dosage to maintain prolactin levels above 100 ng/mL. Because the patient needed to be in a pseudo-postpartum state, progesterone was discontinued on day 123 of treatment and the estrogen dose was reduced to 4 mg. Domperidone (80 mg) was continued to maintain hyperprolactinemia. After day 123, as progesterone and estrogen levels decreased, milk secretion increased, as physiologically is the case with milk secretion during the postpartum period, with approximately about 30 ml of milk per day.

There is no protocol for inducing lactation in transgender women, but protocols for inducing lactation in cisgender women are well known. For example, the Newman-Goldfarb protocol aims to simulate the hormonal fluctuations of pregnancy and prepare the breasts for lactation [13]. This protocol involves increasing prolactin levels with a galactagogue, while concurrently raising progesterone and estrogen levels, followed by a decrease in the latter two during the postpartum period. Estrogen, progesterone, and domperidone levels were adjusted based on this protocol to achieve blood levels ranging from high estrogen, high progesterone, and high prolactin (pseudo-pregnancy) to low estrogen, low progesterone, and high prolactin (pseudo-postpartum state) (Fig. 1).

Changes in hormone levels during treatment

The levels of progesterone, estradiol, prolactin, and testosterone in blood were measured on days 0, 73, 85, and 135 of treatment

On day 146, her partner delivered and the patient was able to directly breastfeed the baby. After consultation with the patient, domperidone was tapered and breastfeeding was discontinued on day 237, 3 months after delivery. The breastfeeding period was physically and psychologically taxing for the patient because of the ongoing hypoestrogenic and hyperprolactinemia associated with drug adjustments. Considering the patient’s age, health, and the burden of raising a newborn, breastfeeding was discontinued. The results of the child’s blood tests at 3 months of age showed no obvious abnormalities and her growth was within the normal range.

Results of analysis of milk composition are shown in Table 2. Protein in the breast milk composition was very high at 123 and 126 days after the start of treatment. The sIgA and lactoferrin levels were high, and calcium and zinc levels were comparable with normal breast milk, but phosphorus levels were low. Breast milk composition at 199 and 215 days of treatment was considered equivalent to that of 7–8 months of gestation and within the normal range compared with known milk data from preterm infants [14, 15]. Note that the results of these measurements were based on 1 day of milk, rather than a session, given the small volume of lactation per session.