Excessive estrogen in circumstances of deficient progesterone induces a decrease in receptor sensitivity. One of progesterone's functions is to restore the normal sensitivity of estrogen receptors. When progesterone is restored, estrogen receptor sensitivity is restored also.
There are a number of studies showing that estradiol can stimulate prolactin production.
Prolactin synthesis in primary cultures of pituitary cells: Regulation by estradiol
Evidence That Autoregulation of Prolactin Production Does Not Occur at the Pituitary Level
Estrogen control of prolactin synthesis in vitro
Prolactin Secretion in vitro
Effects of Gonadal and Adrenal Cortical Steroids.
Effects of Estradiol and Progesterone on Plasma Gonadotropins, Prolactin, and LHRH in Specific Brain Areas of Ovariectomized Rats
During pregnancy women produce Estetrol (E4), or 15α-hydroxyestriol, an estrogen steroid hormone, found in detectable levels in maternal serum at around week 20.
Estetrol reaches the maternal circulation through the placenta and was already detected at nine weeks of pregnancy in maternal urine. During the second trimester of pregnancy high levels were found in maternal plasma, with steadily rising concentrations of unconjugated E4 to about 1 ng/mL (> 3 nmol/L) towards the end of pregnancy. So far the physiological function of E4 is unknown. The possible use of E4 as a marker for fetal well-being has been studied quite extensively. However, due to the large intra- and inter-individual variation of maternal E4 plasma levels during pregnancy this appeared not to be feasible.
Since 2001 E4 has been studied extensively. High oral absorption and bioavailability with a 2–3 hours elimination half-life in the rat has been established. In the human E4 showed a high and dose-proportional oral bioavailability and a long terminal elimination half-life of about 28 hours.
Results from in vitro studies showed that E4 binds highly selective to the estrogen receptors with preference for the ERα form of the receptor unlike ethinyl estradiol (EE) and 17β-estradiol (E2). Also in contrast with EE and especially with E2, E4 does not bind to sex hormone binding globulin (SHBG) and does not stimulate the production of SHBG in vitro.
The properties of E4 have also been investigated in a series of highly predictive, well validated pharmacological in vivo rat models. In these models, E4 exhibited estrogenic effects on the vagina, the uterus (both myometrium and endometrium), body weight, bone mass, bone strength, hot flushes and on ovulation (inhibition). All these effects of E4 were dose-dependent with maximal effects at comparable dose levels. Surprisingly, E4 prevented tumour development in a DMBA mammary tumour model to an extent and at a dose level similar to the anti-estrogen tamoxifen and to ovariectomy. This anti-estrogenic effect of E4 in the presence of E2 has also been observed in in vitro studies using human breast cancer cells [in-house data Pantarhei Bioscience B.V., The Netherlands].
The data indicate that E4 may be suitable for use in several indications e.g. contraception, hormone replacement therapy (both vasomotor symptoms and vulvar vaginal atrophy), breast cancer and osteoporosis. Estetrol is being developed as estrogenic component in the oral contraceptive pill by Estetra (Belgium). Pantarhei Bioscience B.V. (The Netherlands) is developing estetrol for hormone replacement therapy, breast cancer and osteoporosis.
High Estrogen Levels While Breastfeeding
During pregnancy, circulating levels of the sex hormones estrogen and progesterone rise to prepare your body for lactation. After you give birth, however, levels of these hormones drop as your body increases production of prolactin. As levels of this lactation-inducing hormone increase with decreasing estrogen levels, high estrogen levels after you give birth may make it difficult for you to breastfeed your baby.
Estrogen and Prolactin
In a typical pregnancy, estrogen levels rise to promote the development of milk ducts in your breasts. While high estrogen levels help to prevent you from lactating during your pregnancy, they also trigger the production of prolactin to prepare you for lactation after giving birth. Once prolactin levels reach a certain point, they prevent the ongoing production of estrogen. As such, estrogen levels typically drop toward the end of your pregnancy as prolactin levels rise, allowing you to breastfeed normally after you give birth.
While they typically drop after you give birth, estrogen levels may remain high despite your body's boost in prolactin production. This may be due to a condition known as estrogen dominance, which involves high levels of estrogen and low levels of progesterone. As these high levels of estrogen mimic those of pregnancy, your body may continue to behave as though pregnant after your body's birth. As such, estrogen dominance may block prolactin's milk-producing abilities, potentially preventing you from lactating after you give birth.
High estrogen levels following pregnancy may arise from exposure to external sources of estrogen or estrogen-like chemicals. These may include hormone-replacement therapies, petrochemicals and solvents, which may be present in cleaning products, cosmetics, soaps and shampoos. Antibiotics, pesticides and growth hormones present in commercially farmed animal products and produce may also contribute to high estrogen levels, because these products can disrupt natural changes in hormone balance. Other causes may include obesity or excess body fat, high fat intake, liver disease, high alcohol consumption, magnesium and vitamin B6 deficiencies, and stress.
Regular exercise may help to lower your estrogen levels by lowering stress and body fat, potentially reducing complications that may arise when trying to breastfeed. Reducing your fat and alcohol intake, eating more foods rich in vitamin B6 and magnesium, and replacing commercially-produced food with organically farmed products may also help to reduce post-delivery estrogen levels. Because these lifestyle changes may not have immediate effects, the use of an anti-estrogen drug, such as the steroid clomiphene, may help to quickly reduce estrogen levels and allow you to breastfeed properly.