Mammoplasia | |
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It is normal for the breasts to enlarge during pregnancy. |
Mammoplasia is the normal or spontaneous enlargement of human breasts. [1] Mammoplasia occurs normally during puberty and pregnancy in women, as well as during certain periods of the menstrual cycle. [2] [3] [4] When it occurs in males, it is called gynecomastia and is considered to be pathological. [4] When it occurs in females and is extremely excessive, it is called macromastia (also known as gigantomastia or breast hypertrophy) and is similarly considered to be pathological. [5] [6] [7] Mammoplasia may be due to breast engorgement, which is temporary enlargement of the breasts caused by the production and storage of breast milk in association with lactation and/or galactorrhea (excessive or inappropriate production of milk). [8] Mastodynia (breast tenderness/pain) frequently co-occurs with mammoplasia. [9] [10]
During the luteal phase (latter half) of the menstrual cycle, due to increased mammary blood flow and/or premenstrual fluid retention caused by high circulating concentrations of estrogen and/or progesterone, the breasts temporarily increase in size, and this is experienced by women as fullness, heaviness, swollenness, and a tingling sensation. [11] [12]
Mammoplasia can be an effect or side effect of various drugs, including estrogens, [2] [13] antiandrogens such as spironolactone, [14] cyproterone acetate, [15] bicalutamide, [16] [17] and finasteride, [18] [19] growth hormone, [20] [21] and drugs that elevate prolactin levels such as D2 receptor antagonists like antipsychotics (e.g., risperidone), metoclopramide, and domperidone [22] [23] and certain antidepressants like selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). [23] [24] [25] The risk appears to be less with serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine. [26] The "atypical" antidepressants mirtazapine and bupropion do not increase prolactin levels (bupropion may actually decrease prolactin levels), and hence there may be no risk with these agents. [22] Other drugs that have been associated with mammoplasia include D-penicillamine, bucillamine, neothetazone, ciclosporin, indinavir, marijuana, and cimetidine. [6] [27]
A 1997 study found an association between the SSRIs and mammoplasia in 23 (39%) of its 59 female participants. [26] Studies have also found associations between SSRIs and galactorrhea. [24] [28] [29] [30] These side effects seem to be due to hyperprolactinemia (elevated prolactin levels) induced by these drugs, an effect that appears to be caused by serotonin-mediated inhibition of tuberoinfundibular dopaminergic neurons that inhibit prolactin secretion. [26] [28] [29] The mammoplasia these drugs can cause has been found to be highly correlated with concomitant weight gain (in the 1997 study, 83% of those who experienced weight gain also experienced mammoplasia, while only 30% of those who did not experience weight gain experienced mammoplasia). [26] The mammoplasia associated with SSRIs is reported to be reversible with drug discontinuation. [30] SSRIs have notably been associated with a modestly increased risk of breast cancer. [31] This is in accordance with higher prolactin levels being associated with increased breast cancer risk. [32] [33]
In puberty induction in hypogonadal girls and in feminizing hormone therapy in transgender women, as well as hormonal breast enhancement in women with breast hypoplasia or small breasts, mammoplasia is a desired effect. [34] [35] [36] [37]
Estrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the major progestogen in the body. Progesterone has a variety of important functions in the body. It is also a crucial metabolic intermediate in the production of other endogenous steroids, including the sex hormones and the corticosteroids, and plays an important role in brain function as a neurosteroid.
Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation and nursing. It is secreted heavily in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the immune system and pancreatic development.
Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.
Amenorrhea is the absence of a menstrual period in a female who has reached reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses during childhood and after menopause.
Hyperprolactinaemia is the presence of abnormally high levels of prolactin in the blood. Normal levels average to about 13 ng/mL in women, and 5 ng/mL in men, with an upper normal limit of serum prolactin levels being 15-25 ng/mL for both. When the fasting levels of prolactin in blood exceed this upper limit, hyperprolactinemia is indicated.
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.
Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis. It raises the level of prolactin in the human body and is used to induce and promote breast milk production. It may be taken by mouth or rectally.
Galactorrhea or lactorrhea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.
Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to reduce the risk of breast cancer in those at high risk. It is taken by mouth.
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as breast tenderness, is usually associated with the menstrual period and is not serious. Pain that involves only one part of a breast is more concerning, particularly if a hard mass or nipple discharge is also present.
Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.
Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate.
Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life.
Galactorrhea hyperprolactinemia is increased blood prolactin levels associated with galactorrhea. It may be caused by such things as certain medications, pituitary disorders and thyroid disorders. The condition can occur in males as well as females. Relatively common etiologies include prolactinoma, medication effect, kidney failure, granulomatous diseases of the pituitary gland, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. Galactorrhea hyperprolactinemia is listed as a “rare disease” by the Office of Rare Diseases of the National Institutes of Health. This means that it affects less than 200,000 people in the United States population.
Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.
A prolactin modulator is a drug which affects the hypothalamic–pituitary–prolactin axis by modulating the secretion of the pituitary hormone prolactin from the anterior pituitary gland. Prolactin inhibitors suppress and prolactin releasers induce the secretion of prolactin, respectively.
High-dose estrogen therapy (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.
An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.
The side effects of cyproterone acetate (CPA), a steroidal antiandrogen and progestin, including its frequent and rare side effects, have been studied and characterized. It is generally well-tolerated and has a mild side-effect profile, regardless of dosage, when it used as a progestin or antiandrogen in combination with an estrogen such as ethinylestradiol or estradiol valerate in women. Side effects of CPA include hypogonadism and associated symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis; breast changes such as breast tenderness, enlargement, and gynecomastia; emotional changes such as fatigue and depression; and other side effects such as vitamin B12 deficiency, weak glucocorticoid effects, and elevated liver enzymes. Weight gain can occur with CPA when it is used at high doses. Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. Few quantitative data are available on many of the potential side effects of CPA. Pooled tolerability data for CPA is not available in the literature.
The cyclic changes of the adult mammary gland can be associated with the menstrual cycle and the hormonal changes that control that cycle. Estrogens stimulate parenchymal proliferation, with formulation of epithelial sprouts. This hyperplasia continues into the secretory phase of the cycle. Anatomically, when the corpus luteum provides increased amounts of estrogen and progesterone, there is lobular edema, thickening of the epithelial basal membrane, and secretory material in the alveolar lumen. Lymphoid and plasma cells infiltrate the stroma. Clinically, mammary blood flow increases in this luteal phase. This increased flow is experienced by women as fullness, heaviness, and turgescence. The breast may become nodular because of interlobular edema and ductular-acinar growth.
[M]any women report breast changes during the normal menstrual cycle, with a feeling of fullness and a tingling sensation immediately before menstruation.1 Women taking oral contraceptives also seem to experience similar breast symptoms.2 It has been claimed that there are also pronounced changes in breast volume during the normal menstrual cycle, with maximum values occurring in the week before menstruation.3