Hormones are like micro SD cards—small yet powerful. They are tiny chemical messengers that are secreted into the blood by organs called glands. They are important for maintaining the internal environment of the body—as well as interpersonal communications and for many even a marriage can be destroyed over hormonal imbalance.
The sex hormones are responsible for a lot more than just determining someone’s sex at birth. They are also responsible for maintaining and regulating the sexual cycle, onset of puberty and secondary sexual characteristics, moods, general health and even immunity.
In this article, we will take a look at the female hormones—the types of sex hormones, the onset of puberty and menstruation, hormonal disorders, PMS, pregnancy along with some interesting new researches regarding hormones and much more.
Types Of Female Hormones
Estrogen and progesterone are two of the most important female hormones, but they are far from being the only ones working in sync to maintain a woman. Apart from them, there are other female hormones as well, which are working to regulate and balance the sexual cycle.
–Gonadotropin releasing hormone (GnRH): released from the hypothalamus, its function is to stimulate the production of the following hormones from the pituitary.
-LH (Luteinizing hormone)
-FSH (Follicle Stimulating Hormone)
As mentioned before, GnRH, is released from the part of the brain called the hypothalamus, and it goes on to act on another part of the brain, pituitary and cause the secretion of LH and FSH. Both these hormones act on the ovaries; without their release, the ovaries would remain silent spectators, as they are during most of a girl’s childhood.
- Hypothalamus → GnRH → Pituitary → FSH → Follicle → Estrogens
- Hypothalamus → GnRH → Pituitary → LH → Corpus luteum → Progesterone
Moreover, they are released in a cyclical pattern and thus their effect waxes and wanes accordingly. Their primary function is to reach the ovaries and stimulate the growth and proliferation of follicles, which are millions of tiny cells in the ovaries, containing the developing eggs. These follicles when mature produce the hormone, estrogen.
Estrogens are of three types, estradiol, estriol and estrone. Estriol is the main estrogen in pregnancy; estradiol is almost always present for maintenance of female reproductive system, and estrone is least abundant of all.
During the cycle, there is a sudden surge in the level of LH, and this causes the developing egg in the follicle to be released in the uterus. Once the egg has released into the uterus, the remaining follicle develops in the corpus luteum and this produces the hormone, progesterone.
Progesterone’s main function is to prepare the uterus for implantation and pregnancy. If no pregnancy occurs, then the corpus luteum disintegrates and no more progesterone is produced, and the egg is removed from the body in the form of menstrual bleeding.
Inhibin: released from the ovaries, this is the hormone that decreases FSH production.
Activin: it works antagonistically to inhibin, i.e. it enhances the production of FSH.
Follistatin: decreases the activity of Activin, by binding to it, and its overall effect is to decrease FSH secretion.
Testosterone is another critical hormone in a woman. In young women, ovaries are responsible for the production of testosterone, which they then convert to estrogen. Other body tissues like skin and peripheral fat also convert other hormones into testosterone. One of the functions of testosterone is to increase vaginal blood flow as well as lubrication. Moreover, it is also responsible for a woman’s libido, and strength, as well as, muscle and bone development. Like other hormones, its levels also vary during the sexual cycle and even during the day, being highest in the morning. Testosterone is also responsible for the distributive pattern of body hair in a woman, and when it is produced in very high levels, it causes hirsutism hence it is even associated with polycystic ovary syndrome.
Puberty And The Menstrual Cycle
The onset of sexual maturation and transformation of a child into an adult, is called puberty. There are a lot of changes in the body including its shape and size, as well as attainment of fertility. The onset of puberty varies in boys and girls, averaging the age of 13 and 11 years, respectively. Usually, girls attain every stage of puberty before boys. While inception of puberty is dependent most certainly on hormones, its onset varies among girls and can only be partly explained by racial, genetic and environmental differences.
Considerable attention is being paid to the timing of puberty because of the relative risk of future disorders like breast cancer, cardiovascular disease, behavioral disorders as well as obesity and metabolic syndrome.
Normal ages of puberty:
a) Girls: 8-13
b) Boys: 9-14
Puberty and menstrual cycle include the following:
Hormonal and physical changes at puberty
Puberty and Sex Hormones Imbalance
Hormonal And Physical Changes At Puberty
Puberty is determined by the hormonal changes and the physical changes in the body. This occurs systematically and one step leads to another.
Hormonal changes at puberty: The part of the brain, called pituitary, can release the brakes on gonad-stimulating hormones (FSH and LH) any time. This means that puberty onset is held in check by the Gonadotropin Releasing Hormone (GnRH) from the hypothalamus.
: Remember, GnRH (from hypothalamus) FSH and LH (gonadotropins) release from pituitary
The changes in the level of gonadotropins are reflective of episodic secretion of GnRH and these changes occur before and during puberty with greater amplitude and with more regularity. The changes in hormones are more so during sleep than during wakefulness and are more exaggerated for LH than for follicle stimulating hormone. The levels of gonadotropins rise slowly and then progressively until the onset of the menstrual cycle in the females. Soon, the increase seen only during sleep, progresses to regular daytime pulses—and this event is heralded by breast development.
Physical Changes At Puberty
All the physical changes at puberty, also called, secondary sexual characteristics, can be attributed to the hormones. This [table] shows some of the physical changes and the stages they occur in, along with the ages.
-Breast development: It is one of the earliest signs of puberty. This occurs secondary to increased gonadotropin and estradiol (estrogen) levels.
–Hair development: It is indicative of increased amount of androgens in the body. There is development of coarse and highly pigmented hair in the pubic region, about 6 months after breast budding. Sometimes, the reverse may be true.
–Onset of menstruation: This occurs slightly late, and usually after the physical changes have occurred. Regular ovulation follows the onset of menstruation.
–Growth spurt: This occurs mainly due to estrogen in girls, which stimulates the maturation of the skeletal system. Moreover, this occurs earlier in girls (at the onset of puberty) than boys; girls show a relatively slower growth spurt during puberty compared to boys who have maximum growth mid-puberty. On an average, this spurt occurs around 11 years of age with an average mean height velocity of 8.5cm per year, and a total gain in height of 25cm during the growth period. The growing period ceases typically at age 15 years in girls and 17years in boys.
–Weight gain: Puberty is responsible for significant weight gain; an estimate of 50% of adult body weight is gained during this time. There is a 6 month difference in peak height and peak weight (which occur later) in girls, with an average gain of 8.3 kg/year at age 12.5 years.
–Fat distribution: Some changes occur in the proportion of fat, bone and muscle in the body and the difference between a male and a female body become more marked. Growth Hormone and Sex steroids (estrogen and progesterone) cause an increase in muscle mass, as well as bone mineral content. The distribution of fat also changes under the influence of hormones and becomes more subcutaneous in females and peripheral rather than central (around hips, buttocks and thighs).
–Development of sexual organs: there is also development and maturation of the female sexual organs; vagina and vulva grow, and under the influence of estrogen there is also maturation of the fallopian tubes and the uterus.
–Acne: It may occur due to the changes in hormones. Pustules—which are pus filled spots— can also occur. These changes are secondary to androgen release.
–Being a teenager: Along with physical changes, there are mental and psychological changes as well with the onset of puberty. This is an emotional rollercoaster ride characterized by the changing hormones and subsequent body changes. Having a low self-esteem, being self-conscious, being aggressive and depressed with unexplained mood swings is common in puberty.
Delayed Puberty is term used if a child has bone age and secondary sexual characters both not achieved by age 15 years. If a girl does not experience periods by age 16, it is termed as amenorrhea. Delay in puberty warrants a mandatory check up by a pediatrician. For amenorrhea, pelvic exam or a USG is the first step in evaluation to look for a uterus. Further investigations include serum FSH levels, karyotyping, serum testosterone analysis.
Start of the ‘period’ or menstrual cycle is the most prominent sign of puberty in girls.
The mechanism of puberty initiation is poorly understood, but clearly, genetic, environmental and physical factors (such as body fat) have an important role. Nutrition is another factor whose role has been underplayed when it comes to sexual maturation; under-nourished children have delayed sexual maturation and late onset of puberty. Furthermore, anorexia is associated with amenorrhea (absence of menstruation) and a decrease in the levels of gonadotropins.
Briefly, menstruation can be described in the following words; the female eggs are contained in the follicles present in the two ovaries which lie on the either side of Uterus. While there are 1-2 million of these eggs at the time of birth, only about 0.3 to 0.5 million remains by the time of puberty. The limitation of these oocytes is that they are not entirely developed and are in different stages of development. During the menstrual cycle, one of these eggs attains maturity (under the influence of hormones) and is released into the uterus for fertilization by a sperm (ovulation). If fertilization occurs then pregnancy results and if no fertilization occurs then menstrual bleeding results.
There are three main phases of menstrual cycle.
Phase 1: Follicular Phase (Day 0-13)
This phase is the initial part of the cycle, where day 0, refers to the bleeding from the previous cycle and low circulatory level of sex steroids—estrogen and progesterone. The low levels of sex steroids signal the pituitary to release the gonadotropins, LH and FSH—the latter secreted more. There is simultaneous release of GnRH in pulsatile fashion from the hypothalamus, which further enhances the signal to the pituitary to release LH and FSH.
FSH is the hormone that recruits the follicles from the ovary and only one follicle matures enough to go into further development—the Graafian follicle. This recruitment occurs during days 5-7 of the cycle, and this recruited follicle also releases estrogen. Subsequently, the level of FSH starts to decline and the level of LH begins to increase. At this point, two hormones are present in sufficient amounts—estrogen and LH.
Phase 2: Ovulation (Day 13-14)
During this phase, there is an amazing interplay between the hormones estrogen and LH. The rise (about 200 picogram) in the level of estrogen causes a surge in the level of LH, and it is this surge that causes the release of egg from the Graafian follicle into the Uterus. Ovulation occurs 36-44 hours after the levels of LH rise. Ovulation marks the completion of this short phase, and it corresponds to the 13-14th day of the cycle.
Phase 3: Luteal Phase (Day 14-28)
During this phase, there is an increase in the level of progesterone i.e. released by the remaining follicle. Remember, we talked about Corpus Luteum before. This fancy word refers to the follicle after the egg has been released from it. The corpus luteum is essential, in that, it is responsible for the production of progesterone. The function of progesterone—apart from increasing the need to eat and sleep—is to maintain the endometrial (innermost lining of uterus) lining so that the fertilized egg can have a cushy endometrium to implant in. It ensures that the endometrial lining is thick and has a good blood supply; this lining can only maintain itself under the influence of progesterone.
Corpus Luteum can only last for 14 days; after this, it stops producing progesterone. If pregnancy occurs, the production of progesterone is taken over by other hormones released (beta-HCG) and corpus luteum can disintegrate. If however, pregnancy does not occur, then progesterone levels decline and the endometrial support diminishes to the point that it starts shedding. This marks the beginning of menstrual bleeding.
At the end of the cycle, there is a decrease in the levels of estrogen and progesterone, which trigger the brain to release FSH and LH, and thus a new cycle is initiated.
This graph shows the variable levels of different hormones during a normal menstrual cycle.
Puberty And Sex Hormones Imbalances:
The Sex hormones in female body have a complicated system and slight imbalance within their ranges have a slight to deep effects in the body. These imbalances include:
Pre-Menstrual syndrome (PMS)
Pre-Menstrual Syndrome (PMS)
It is impossible to talk about the menstrual cycle, and not talk about PMS. Jokingly (but most inaccurately) referred to as Pissed at Men Syndrome, by men, this is the time of mood swings, anxiety/depression, being short tempered and food cravings etc. before menstruation. In the last 30 years, there has been increased awareness about PMS amongst women, their partners and the media.
While worldwide it is not considered a dangerous entity, this is not the case in the US and Australia. In fact, the American College of Obstetricians and Gynecologists (ACOG), the American Psychiatric Association, as well as The National Institute of Mental Health (NIMH) provides not only research grants for this disorder, but also evidence-based guidance to the clinicians.
PMS has been researched upon through the ages, and in-fact Hippocrates was amongst the first people to recognize it and refer to it as “agitated blood” which makes its way from uterus whence it is expelled.’ Beyond that, it was acknowledged by Trotulo of Salerno and another Italian, Giovani da Padua and later by the English physician James Prichard who used the words ‘…capricious temper…moroseness in disposition…A proneness to quarrel…’ for it.
PMS can present with both, behavioral symptoms, and physical discomfort. These can include anxiety and depression, poor concentration, mood swings, insomnia, food craving, headache, bloating, constipation, joint pain, fatigue and fluid retention.
When the symptoms of PMS become severe enough to be disabling, then it is referred to as Premenstrual Dysphoric Disorder (PMDD).
The First Advice for a patient suspected to be suffering from PMS is to maintain a menstrual diary, noting down days of onset of symptoms and day of onset of a period. Through continued research, a link between PMS symptoms and ovulation has been established. For this reason, in the US, treatment of PMS advocated by gynecologists includes the use of oral contraceptive pills, as opposed to intrauterine device Levonorgestrel in the UK. Moreover, psychiatrists from the USA and Canada, as well as, Swedish researchers favor the use of anti-depressants called SSRIs (Selective Serotonin Re-uptake Inhibitor) for the management of PMS.
Pain experienced during the periods when it is severe is known as dysmenorrhea. It can lead to dysfunctioning of life during the days of periods.
First line treatment is NSAIDS. If it does not relieve by NSAIDS, OCPs (oral-contraceptives) are usually prescribed.
Disorders Of Puberty
The puberty disorders range from ages to ethnicities and races to geographical locations. So there is no definitive point from where hormonal imbalance would be considered as a puberty disorder.
Onset of secondary sexual characteristics like breast development, pubic hair growth, enlargement of testes, which occurs earlier than usual, is called precocious puberty. In technical terms, it is puberty i.e. occurring 2.5 standard deviations below the mean (average). Although medical professionals do not have a consensus regarding the age of precocious puberty, it is generally regarded below age of 8y for Caucasian girls and 7y for African American girls. In boys, precocious puberty is considered, if changes occur before 9 years of age.
Some forms of precocious puberty include:
Cerebral Precocity: in which the hypothalamic diseases/abnormal growths are the causative factors.
Premature Thelarche: is early breast development, which occurs as a standalone disease and is usually transient. Breast development occurs from estrogen from the ovaries.
Premature Adrenarche: is the development of pubic hair prematurely in both girls and boys at the age of 6 years. ‘The maturational increase of androgen production’ that results into an increase of DHEA-S bio-chemically is the pre-mature adrenarche. This is more common in girls and is usually not associated with other changes. It has a relation with obesity and can be due to high level of androgen hormones in the body.
Precocious puberty is much more common in girls as compared to boys. In the case of girls, the cause is mostly idiopathic and not associated with any medical disorder; however, precocious puberty in boys is usually associated with some organic cause. Idiopathic precocious puberty is a diagnosis of exclusion; in such cases there is no apparent cause for the early development of breasts or the unexplained growth spurt or pubic hair development, at a young age. Mostly, such cases are considered normal and could even be familial.
However, it is not a condition to worry about. In the US, less than 5% girls had precocious puberty about one generation ago; today this percentage has increased to more than 10%. In a recent study (part of the Breast Cancer and the Environment Research Program), published in Pediatrics, it was found that more than 10 percent of Caucasian girls had early breast development by the age of 7 years; this percentage was 15% in Hispanic girls and about 25% in girls of African American descent. By the age of 8 years, these rates were even higher.
It seems that the decrease in mean age of puberty has been occurring for the last 150 years, but this age is approaching its biological limit. Not only in the US and Canada, but worldwide, this phenomenon of early maturation is being seen. Interestingly, evolutionary biologists believe that this early age of puberty is similar to the age of maturation in early hunter-gatherers. According to them, late onset of puberty resulted from poor nutrition and poor health. In her book The Falling Age of Puberty in US Girls (2007), author Sandra Steingraber also corroborates that decline in the age of puberty is likely due to better nutrition and health facilities, as well as the ability of women to adapt themselves sexually in accordance with the environmental cues—food, shelter and health.
Research conducted on the behavior of teenagers with precocious puberty has found that early puberty does influence adolescent risk behaviors, with males having a more aggressive approach and fighting problems. Moreover, it was found that early puberty also predicted drug use, alcohol consumption, smoking in age group <14y and sexual debut <16y. For this reason, it is important that parents, teachers and caregivers are trained to have a conversation with their children who are undergoing early puberty, so that their children can deal with certain aspects of their sexuality, successfully. Furthermore, it is important for parents to develop emotional closeness with their prematurely developing daughters to help guide them better in life and help them embrace their womanhood.
Delayed puberty, as the name implies, is puberty onset after the age of 15 in boys and 13 girls. Although what most adolescents experience is a constitutional delay of puberty (CDP) and in time there is full sexual maturation, however, it is important in all cases to rule out an organic cause, as many genetic and syndromic disorders present initially with delayed puberty. Moreover, it is important to provide these children with psychological and emotional support because they may be subjected to ridicule and condescension at the hands of their peers. In such cases therapy with low-dose sex steroids may be appropriate.
There are many causes of delayed puberty, but they are mainly subdivided into very high gonadotropins (hyper-gonadotrophic hypogonadism) or very low gonadotropins (hypo-gonadotrophic hypogonadism), [of which CDP is a part], and FSH and LH resistance.
Hyper-gonadotrophic hypogonadism can be further caused by chromosomal abnormalities, trauma, prior surgery or radiation exposure, chemotherapy, autoimmune disorder, chronic diseases like cystic fibrosis, diabetes, kidney disease etc. Nutritional disorders like anorexia, also cause delayed puberty.
Treatment of delayed puberty constitutes determining the cause and eliminating it accordingly. For CDP, as mentioned before, treatment is sex steroids starting from low dose to high dose—estrogen in girls and testosterone in boys, for 4-12 months. It must be mentioned here that treatment of CDP, has no effect on the final height of the adolescent. Moreover, regular clinical evaluation is necessary to monitor the progression of puberty.
A research about the effect of physical activity and diet on puberty has determined that there is a delay in the sexual maturation and growth of female athletes with strenuous training periods averaging 22 hours/week. In comparison, female athletes with less strenuous training period of about 8 hours/week had little to no effect on puberty.
Pregnancy And Hormones
Pregnancy is a state of constant hormonal overload—and thus there are all the more chances of a ‘hormonocide’.
Pregnancy is the event that occurs when the oocyte or egg released from the ovary during ovulation, meets a zealous sperm. This is called fertilization and it occurs about 48 hours after ovulation. The innermost lining of the uterus, i.e. called the endometrium, has been readied by estrogen to receive this fertilized egg. The endometrium is stabilized by progesterone which is being released by the corpus luteum. After about a week of fertilization, the conceived embryo is implanted in this endometrium. Within 24hours of implantation, beta-HCG production starts by the embryo; this is the hormone that is detected by over-the-counter pregnancy tests. A very high rise in HCG, very early in pregnancy can indicate a trophoblastic tumor whereas an abnormal rise can point to a non-viable pregnancy. For the first six weeks of pregnancy, the corpus luteum produces progesterone, but this role is taken over by the feto-placental unit from the seventh week onwards. The feto-placental unit also produces estrogen.
Hormones are also responsible for the physiological adaptations in the mother’s body especially during the first trimester; there are significant changes in the thyroid, adrenal and pituitary glands, with varying concentrations of the hormones they produce—cortisol, growth hormones, T3 and T4, prolactin etc. These changes are influenced by the placental hormones, HCG, liver and kidneys.
This [table] shows some of the physiological changes in the hormones during pregnancy.
The adaptations in these hormones are meant to meet the body’s needs during pregnancy. In fact, some of the discomforts of pregnancy are due to these physiological changes. For instance, increasing HCG levels can cause changes in appetite, and food tolerance. HCG, along with T4 has also been associated with nausea and vomiting in the first trimester. Progesterone is associated with increased sedative effect and is responsible for the altered sleep pattern; it is also associated with inhibition of contraction of the uterus until the baby is ready for delivery at term. In preparation of lactation, the level of prolactin is also increased during pregnancy. Other hormones from the pituitary gland also increase, including melanin stimulating hormone (MSH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH). Since, the metabolic demands of the body increase during pregnancy, hormones such as T3, T4 and cortisol (released from the adrenals, due to high ACTH), increase to meet it.
The high level of estrogen during pregnancy helps to prepare the body for lactation through breast development, as well as, help the uterus increase in size and vascularity. Moreover, estriol (a type of estrogen) indicates fetal well-being.
Labor: At the end of pregnancy, the initiation of the labor process is also influenced by hormones. Maternal estrogen levels are responsible for the activation of labor through formation of oxytocin receptors in the uterus. However, the estrogen levels in the mother are influenced by the fetal cortisol levels, which interestingly are directly proportional to estrogen. When oxytocin receptors are stimulated by the short bursts of the hormone itself, the uterus begins to contract and as labor progresses; there is more oxytocin release and more regular contractions.
Postnatal: At the end of birth, and with the expulsion of placenta, there is a dramatic decrease in the level of circulating hormones. Most importantly, however, there is combined effect of prolactin and oxytocin on the breast tissue, due to a decrease in the level of estrogen, which allows milk production and secretion. Another effect of oxytocin is that it decreases blood loss by maintaining the contraction of the uterus during puerperium.
After the delivery of the baby, the endocrine system slowly comes back to its original form. This time is also a very emotional time for the mother because of the fluctuating hormones and the resultant physical changes. This is called postpartum depression.
Sexual Hormone Disorders And Their Treatment
Hormonal disorders are common in women due many factors like; genetic dispositions, synthetic food intake, excessive chemical use, high disease prevalence, environmental pollution. The sex hormonal disorders often result into infertility or difficulty in conception. It can also lead to various other diseases like, hyper tension, diabetes, breast and uterine cancer.
The inability to conceive after one year of unprotected sexual intercourse, is known as infertility. The causes of infertility can be many, and therefore complete workup of both the man and the woman, by a team of gynecologist, endocrinologist as well as andrologist must be carried out.
40% cases of infertility can be attributed to female causes. These causes can range from tubal pathologies like Pelvic Inflammatory Disease (PID) to endometriosis, ovulatory disorders and hypogonadism. Every part of the physiology of reproduction is examined to find out the cause of infertility. It can lie in the ovaries (PCOS), Fallopian tubes (PID, tubal blockage, and chlamydia), uterine dysfunction (fibroids), cervical or vaginal cause (hostile cervix, gonorrhea).
In the other 30-40%, the male factors can be the cause of infertility. Untreated hypogonadism in the males can cause decreased sperm count; other causes of infertility can include testicular tumor, vas blockage due to previous STD, testicular torsion, low androgen levels, chemo/radiotherapy, chronic kidney disease, sickle cell disease, chronic liver disease as well as increased levels of prolactin hormone.
The workup of infertility in a woman includes: pelvic ultrasound, hysteroscopy, and vaginal swabs, hormone levels (estrogen, progesterone, and prolactin). In a man, the workup can include: semen analysis, testicular biopsy and hormone levels (FSH, LH and Testosterone).
The treatment of infertility starts with counseling of the patients. If the workup reveals any pathology, then it should be dealt with accordingly. In women with hypogonadism, ovulation can be induced with exogenous estrogen administration. In vitro fertilization (IVF) and Intra cytoplasmic sperm injections (ICSI) are treatments used when no cause can be found or there is a tubal blockage or decreased sperm count.
A study published in May,2016 in New England Journal of Medicine, endorses the previous studies that infertility rates are hard to change with the weight fluctuation. In case of infertility, weight loss has no significant effect other than recommended treatment plan.
Polycystic Ovary Syndrome (PCOS)
This syndrome is a triad of infertility, amenorrhea and hirsutism, and is one of the most common endocrine disorders in the women of reproductive age group. In the US, PCOS is diagnosed from biochemistry (excessive androgen levels) rather than polycystic ultra-sonographic picture of the ovaries, as is done in Europe.
A study published in the American Journal of Obstetrics and Gynecology (ACOG) found that women experiencing PCOS symptoms but physicians prescribe them less sensitive hemoglobin A1C test, which is weak for PCOS detection; rather 2-hour glucose tolerance test and a fasting lipid profile are the two determining tests to find out the metabolic condition of the female with PCOS.
It was found that the women experiencing various symptoms of PCOS such as irregular menstruation, acne, weight gain and infertility are unable to get the exact screening tests for blood sugar and cholesterol which could help prevent the risk of serious metabolic diseases in these women.
PCOS presents with hirsutism, weight gain, amenorrhea and infertility. Hirsutism, related to PCOS, begins with the onset of menstruation and slowly progresses. There is concomitant weight gain in patients as well, with truncal obesity and even insulin resistance. The latter can sometimes present with acanthosis nigricans, which are dark lines in the region of neck, axilla or groin. Irregular menstruation is also a feature of PCOS; however, there can be hirsutism alone in some cases.
The diagnosis of PCOS needs a variety of investigations (Kumar, 2012). These can include: serum testosterone level, androgen levels, estrogen levels, prolactin levels, level of gonadotropins, and ovarian ultrasound. Eventually, PCOS is established according to Rotterdam criteria 2003, if there are two of:
- Biochemically proven increased androgen levels
- Decreased menstruation
- Polycystic appearance of ovaries on ultrasound
The treatment of PCOS includes individual treatment of the symptoms. For PCOS treatment; life style modification is required.
Exercise helps fight PCOS because with exercise the insulin resistance reduces. This way the hyperandrogenism can be minimized.
Irregular menstruation can be treated by cyclical administration of estrogen/progesterone. Insulin resistance is treated by giving the drug Metformin; this drug also improves other symptoms of PCOS.
Symptoms of infertility improve with Metformin; in cases that metformin does not work; the administration of Clomifene can induce ovulation. It is given on day 2-6 of the menstrual cycle but it has its limitation, in that it cannot be used for longer than six cycles.
All treatments must be initiated by a registered healthcare provider and should not be started by the patient herself.
Latest researches published in NEJM said women PCOS have better chance to fertility when the embryo is frozen rather than fresh embryos. In the journal Clinical Endocrinology & Metabolism a research study was published claiming that women with PCOS can be treated against infertility with soy.
Hypogonadism And Estrogen Deficiency
Any reason leading to the decrease in ovarian function would result in estrogen deficiency and its associated symptoms. Hypogonadism, can be secondary or it can be primary. Primary hypogonadism refers to the disease lying in the ovaries themselves; while secondary refers to pathologies that lie elsewhere, for instance, a decrease in LH and FSH from the pituitary. The latter can be due to any reason, like trauma, surgery, tumor, or infection.
Estrogen deficiency, associated with hypogonadism can present with small breasts, dry vagina, lack of menstruation, osteoporosis, thinning/loss of pubic hair and even small and underdeveloped uterus and fallopian tubes.
Treatment of this disorder depends on the cause; certain investigations would be carried out by your healthcare provider, like hormone levels, ultrasound, and MRI of brain (if need be). Only after determining the cause, the treatment would be started with exogenous hormones if they are deemed necessary.
The absence of periods due to disruptive menstrual cycle, is called amenorrhea. This is the commonest gonadal disease in the females. Many diseases present with amenorrhea; these include PCOS, ovarian failure, stress, chemotherapy, increased prolactin hormone, hypothyroidism, increased androgen hormones, pregnancy, uterine or vaginal abnormality, weight-related amenorrhea, dysfunction of the hypothalamus/pituitary, exercise-induced amenorrhea, post-pill amenorrhea. All the causes of amenorrhea need a workup for diagnosis, only then can amenorrhea be treated appropriately. This workup can include: FSH/LH, prolactin and estrogen level, MRI of brain, biopsy of the ovaries, level of thyroid hormone T3 and T4, ultrasound of abdomen and pelvis, hysteroscopy (uterine examination with a camera).
Treatment would depend on the cause and can require exogenous long-term estrogen administration. For other disorders like hypothyroidism, Thyroxin replacement can be needed. Body weight maintenance is also needed and for this purpose a nutritionist can be consulted as well.
Hirsutism refers to excessive facial and body hair. Normally, there is a considerable variation in the distribution of body hair in different women. However, the hair in the beard, breast, chest, axilla, moustache and pubic and thigh region is dependent on sex hormones. Excessive hair in these regions, therefore, can be indicative of increased androgens, either by the ovaries or the adrenals. PCOS is another common cause of hirsutism.
The treatment of hirsutism includes: local treatment as well as systemic treatment. Local treatment includes waxing, bleaching or plucking of excess hair. Electrolysis or laser therapy is also used electively.
Medicines which are used to treat hirsutism require at least a year of treatment for maximal benefit. Some of these medicines are: exogenous estrogen administration, anti-androgens like Cyproterone acetate (given for the first 14 days of menstrual cycle), spironolactone, finasteride etc. It must be mentioned here that all medication must be taken under the guidance of your healthcare provider as they can produce serious side-effects if taken without supervision.
Sex hormones intricacies and their balance is a topic of interest for the scientist. New researches are going on regarding different aspects of the female hormones.
Sex Hormones And Immune System
Immune system is necessary for the defense mechanism of the body against foreign bodies and germs. However, it does not work in isolation; rather, it is dependent on and is influenced by many factors such as the sex hormones, neuroendocrine peptides and other peptides.
The effect of sex hormones on the immune system is that it increases their number, either by producing new cells from the bone marrow or directly increasing their proliferation. Moreover, it is also established that certain types of immune cells such as monocytes, dendritic cells as well as the, T and B lymphocytes have estrogen receptors; which means that estrogen can act on these immune cells through these receptors. Because of their nature, sex steroids can also integrate themselves into the cell membrane (the outermost layer of a cell) of immune cells and thus alter the membrane properties.
During pregnancy, progesterone receptors on the lymphocytes (another type of immune cell) increase and the eventual effect, through a lot of intermediate cells and factors, is to exert an anti-abortive effect. Apart from pregnancy, the immune system also shows variation due to the influence of hormones even during a normal menstrual cycle. It was found in a study that women in the age group of 18-25y, showed an increase in TLC (total leukocyte count) during proliferative and secretory phases of the menstrual cycle.
In conclusion, it was found, that women have a stronger immune system with reduced incidence of certain tumors, viral infections, parasitic infestations and increased resistance. This dimorphism in immune function can be attributed to the endocrine system and hormones. These include: sex steroids, prolactin, growth hormone and adrenal hormones, with estrogen and progesterone leading to hormonal interaction and immunological dimorphism.
Impact Of Caffeine On Sex Hormones In Pre-Menopausal Women
A research study on the effect of caffeine on sex-hormones was carried out, with more than 250 multi-racial participants, and they were followed for 2 menstrual cycles and 8 visits/cycle for hormonal assessment. The reported results were that in white women, caffeine intake of >200mg/day was inversely proportional to free estradiol levels.
On the other hand, women with Asian descent, had positive association of caffeine intake of >200mg/day with free estradiol levels. Green tea intake as well as caffeinated soda intake of >240ml/day in all races showed a positive relation with free estradiol concentration.
Sex Change And The Effect Of Sex Steroids On Adult Brain
Sex hormones, among other things, are also involved in the sexually-dimorphic development of the brain. Researchers from Holland studied the effect of cross-sex hormones administered to transsexuals in early adulthood and their effect on brain morphology.
Effect of estrogen + anti-androgen administration in male-to-female transsexuals, and androgen + anti-estrogen therapy in female-to-male transsexuals, determined that in the former, treatment decreased the brain volume, while in the latter, it increased brain and hypothalamus volumes. This was confirmed through Magnetic Resonance Imaging before and after therapy. It was thus concluded, that sex hormones throughout life, are responsible for organizing and developing the sexual-dimorphism in the human brain.
Another research published in Biology Psychiatry also found that during the sex modify the hormonal treatments change the brain chemistry.
Menopause: Onset & Features
Menopause occurs at about 45 to 55 years of age, and in the US, is used to refer to both the last menstrual period, as well the transitional period before it. The World Health Organization, however, describes it as complete cessation of periods for one year.
Kumar (Kumar, 2012) describes this process as FSH and LH increase, influenced by the diminishing follicles, and eventual estrogen decrease.
Initially, the level of FSH rises followed by the increase in LH. However, estrogen level decreases, due to the decreasing follicles. This leads to disruption of the menstrual cycle and can present clinically as either increased bleeding, a complete absence of bleeding, or scanty irregular bleeding. Eventually, the FSH and LH levels become high enough (>25U/L and >50U/L) that a steady low level of menopausal estradiol is established.
Premature menopause can occur secondary to chemotherapy, radiotherapy, and ovarian disease or surgery.
Features: Menopause can be a very trying time in the life of a woman, and she requires a lot of psychological support from her family and her friends to deal with the sudden physical and mental changes. The clinical features of menopause can vary in different women, however, the commonest symptoms are (Kumar, 2012): vaginal dryness, loss of libido, weight gain, hot flashes (the telltale sign of menopause), depression, anxiety, mood swings, sagging of breasts, sleep disturbances, aches and pains, dry skin, bladder problems, irritability and low self-esteem. Another important change that occurs in the body of a woman is the loss of bone mineral density; this is especially important in the ten years following menopause and is referred to as osteoporosis. It occurs due to the lack of estrogen. The risk of development of Ischemic heart disease also increases.
In today’s era, a woman undergoing menopause has a lot of treatment choices. A lot of improvement in the menopausal symptoms can be achieved with the help of dietary modifications, exercise, yoga and meditation, counseling, nutritional supplements and hormone replacement therapy (HRT).
Menopause And Osteoporosis
Osteoporosis is the decrease in bone quality and bone mineral density and a disruption of its microarchitecture causing increased fracture risk and increased bone fragility.
Osteoporosis occurs due to excessive bone loss, which occurs secondary to reduced ovarian function and decreased estrogen production. Bone formation and resorption are two processes that occur side by side in a normal individual. Estrogens are responsible for maintaining the balance between these two processes so that excessive bone resorption does not take place. Moreover, it suppresses bone turnover by affecting the cells responsible for it—osteoblasts. Estrogens increase the lifespan of these bone forming cells and simultaneously induce the bone-destroying cells—osteoclasts—to die. The deficiency of estrogen, on the other hand, causes increased production of cytokines whose primary function is resorption of bone.
Nutritional factors, such as vitamin D insufficiency, and subsequently reduced calcium absorption also play a major role in osteoporosis. 60-90% of postmenopausal women experience vitamin D levels below 30ng/ml; this factor combined with insufficient calcium intake (<800mg/day) favors osteoporosis and bone loss. Increase in the intake of vitamin D and calcium along with sufficient protein intake can result in reduced cases of hip fracture.
Hormone Replacement Therapy (HRT)
This refers to the treatment of menopause and its symptoms through the administration of exogenous hormones—both estrogen and progesterone. These treatments not only help improve the symptoms in peri-menopausal women, but also help prevent bone loss. However, this treatment, just like any other, is not without risks.
John Studd, at the Menopause Clinic at Kings College Hospital in London, sheds light on HRT, in the following words, sex hormones in adequate amounts keep women, “out of the orthopedic wards, the divorce courts and the madhouse.”
Using HRT is a personal choice; not every healthcare provider endorses it due to certain risk factors associated with it. Moreover, its use also depends on the severity of the menopausal symptoms. The table below shows some of the benefits vs. risks of HRT.
[TABLE] from Kumar and Clark
Large clinical trials have been held to examine the long-term effects and benefits of HRT. These include the Heart and Estrogen/Progestin Replacement Study follow-up (HERS II), Women’s Health Initiative (WHI) as well as its ancillary study Women’s Health Initiative Memory Study (WHIMS).
The HERS trial did not find a reduction in the risk of Coronary Heart Disease in women taking HRT. The next study, WHI was terminated, because it was discovered in the follow-up, that the administration of estrogen and progesterone together, was associated with an increased risk of breast cancer. Moreover, worsened cardiovascular outcomes like pulmonary embolism, chronic heart disease, and stroke were also noted, though the incidence was not high enough to show that disease specific boundaries were crossed. However, there was an overall reduction in the risk of hip fractures in women taking HRT, due to increased bone mineral density.
In the WHIMS study, it was revealed that in women taking combined HRT, there was an increased risk of dementia and no effect on cognitive decline; thus the idea that HRT could be used to prevent dementia, was rejected.
It seems, from another study (Nurses’ Health Study), that the timing of beginning HRT is critical and to reap the benefits of HRT, the therapy should be commenced near menopause, rather than after menopause. The most recent data released from this study shows that there is in fact reduced risk of Chronic Heart Disease in women who took HRT near menopause.
The Third Gender and Issue of Inter-Sexuality Determination:
The third gender is the disorder of sexual differentiation and occurs due to chromosomal abnormalities. Normally there are 46 chromosomes in human beings, 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes. It is this pair of sex chromosome that determines whether the person is a girl or a boy.
Girls have XX chromosomes, while boys have XY chromosomes. Abnormal differentiation can result in chromosomal abnormalities which can affect the sex of the person.
Some of the Defined Disorders are:
Turner’s Syndrome: In this disorder there are 45 chromosomes with a single X chromosome—45X. They appear as female but have only a streak of ovaries.
Klinefelter’s Syndrome: There are 47XXY chromosomes. They appear as males but have small testes.
Anorchia: It is the absence of testes. They have 46XY chromosomes and appear as immature females.
Some Unusual Cases:
NEJM published that female with ‘pure gonadal dysgenesis’ had no periodic cycle and hypoplasia of ovaries but rest of the Turner’s syndrome defines features were absent. The XY was the sex chromosomal pattern but surprisingly fallopian tubes, vagina and uterus were present. The turner’s syndrome with mosaicism with XX and XO sex chromosomes were also presented.
The mosaicism in true hermaphrodite (third gender) showed a mixture of XY and XO sex chromosomes.
The inter-sex are the individuals who have underdeveloped sex organs and their sex hormones have been altered due to genetic reasons. Y. Marshall, University of Southampton, UK, in his book ‘intersex in the age of ethics’ is of the view that the relation between the sexual practices, anatomy and sexual identity is crucial because inter-mingling can only be defined in black and white, if the above mentioned relationship’s boundary is explained completely.
Intersex issues and the Olympics had made women athletes to go through indiscriminate scrutiny. Few of the athletes, who had a masculine appearance, when tested for hyper-androgenism (testosterone levels) were found to be having testosterone levels higher than the females but lower than the males. IAAF decided to let intersex participants play in the categories, in which they have been raised from the birth. This step was taken to avoid the attempts to endorse sharp sexes.
Myths About Female Hormones
Every Woman Suffers From PMS: PMS symptoms can be different for different women. For many, PMS simply doesn’t exist. Many women go through the pre-menstrual time without a growl or a grimace. There are many other factors responsible for PMS than just plummeting estrogen levels. For instance, stress from work is what can be causing your headache and dropping mood—PMS might not be the cause.
Women Living In Proximity Can Have Syncing Of Menstrual Cycle: This myth was busted by a 2013 study published in Journal of Sex Research. It proved that there is no such thing as menstrual synchrony and any syncing is merely a chance. However, it does sound fascinating, to have synced menstrual cycles.
Menopause Occurs At An Age Of 50 Years: Nobody’s ovaries have a time clock that tells them that their 50 years are up. Menopause can begin at any age between 45-55 years. In an average woman, it occurs at 52y. Because menopause symptoms begin earlier—peri-menopausal time, you can still be menstruating and experiencing hot flashes at the same time. Even the peri-menopause period can last from a few months to a year.
Weight Gain Is A Must In Menopause: Many women gain a lot of weight during menopause, thinking that it is inevitable. Despite the fluctuations in hormones which do affect weight, it is not an inevitable phenomenon. Infact, with proper diet and exercise, this weight gain can be easily controlled.
Allergies Do Not Affect Hormones: Hormonal balance can certainly be affected by allergens—particularly food allergens (Guton, 2000). This is because of the production of a special factor called IgG reaction (immunoglobulin G) which can take a long time to take effect and a single exposure can last for as long as 6 months.