Page 98-107, 118-123, 16 pages Page 1 of13
Chapter 5: Sex Hormones, Sexual Differentiation, Menstruation
• Hormones are powerful chemical substances secreted by endocrine glands into the bloodstream,
exerting effects relatively quickly and systemically. The gonads testes and ovaries secrete testosterone
(and 5-alpha dihydrotestosterone, DHT, both androgens), and estrogens and progesterone.
• The hypothalamus is a region of the brainstem which regulates many vital behaviours such as eating,
drinking, and sexual behaviour. It also regulates the pituitary gland, the anterior lobe of which interacts
with the gonads.
• The adrenal gland also produces these sex hormones
Sex Hormone Systems in Males
• Testosterone is a masculinizing sex hormone, which has important
functions in stimulating and maintaining secondary sex
characteristics (e.g. facial hair), maintaining genital tissues and
spermatogenesis, sex drive, and stimulating the growth of bone and
muscle (anabolic effects)
• The pituitary gland produces the gonadotropins follicle-stimulating
hormone (FSH) and luteinizing hormone (LH). FSH controls sperm
production, and LH testosterone production.
• LH and FSH levels are regulated by gonadotropin-releasing
hormone (GnRH), secreted by the hypothalamus. The feedback loop
of the HPG hypothalamus-pituitary-gonad axis regulates sex
• This cycle is a negative feedback loop – LH stimulates testosterone
production, but if testosterone levels are too high, hypothalamus
reduces GnRH, thus reducing LH and testosterone.
• Men also display cycles of testosterone: men have day-to-day
mood changes, weekly fluctuations in testosterone levels, seasonal
fluctuations with higher levels in spring/summer, and men with a female partner have a 28-day cycle
which may be synchronized with their partner’s.
• Social Effects on Testosterone: Social neuroendocrinology, reciprocal relationships between social
interactions and hormones.
o Professional female wrestlers’ testosterones ↑ after competition.
o Men who respond to infant doll’s crying with nurturing responses have testosterone levels
• Inhibin is another hormone produced by the testes in Sertoli cells, acting as negative feedback for FSH
Sex Hormone Systems in Females
• Estrogen is responsible for feminizing the body by: stimulating the growth of the uterus and vagina,
enlarging the pelvis, and breast growth in puberty. It also contributes to the menstrual cycle by
maintaining the mucous membranes of the vagina, and stops growth of bone and muscle.
• Levels of estrogen and progesterone fluctuate according to phases of the menstrual cycle and to
events such as pregnancy and menopause.
• FSH regulates follicle and ovum development, while LH stimulates ovulation; both help maintain levels
of estrogen and progesterone
• Similar negative feedback loop of hypothalamus, pituitaries, and ovaries as in the male. Inhibin is also
produced by the ovaries to inhibit FSH production. Page 98-107, 118-123, 16 pages Page 2 of13
• The pituitary produces prolactin, and the hypothalamus oxytocin. Prolactin stimulates milk production
in the mammary glands after childbirth, while oxytocin stimulates ejection of milk from the nipple as well
as uterine contractions during childbirth. Oxytocin also seems to promote affectionate bonding
• Human chorionic gonadotropin (hCG) is produced by the conceptus and placenta, indicating
• Estrogen and progesterone are steroid hormones, while LH, FSH, GnRH, prolactin and oxytocin are
The Menstrual Cycle
• Very few species have menstrual cycles (apes, monkeys), with most having estrous cycles
o There is no menstruation, only slight spotting
o Ovulation occurs during estrus (“in heat”) alongside spotting while in the menstrual cycle
ovulation occurs midway between periods of menstruation
o Animals with estrous cycles engage in sexual behaviour only during estrus phase, while with
menstrual cycle females can engage in and enjoy sexual behaviour throughout cycle
Phases of the Menstrual Cycle
• Menstruation is biologically the last phase, but the first day of menstruation is numbered as day 1
• 1) Follicular Phase:
o Pituitary secretes ↑FSH, stimulates a follicle to bring an egg to maturity. Process of primordial
follicle maturation takes 3 months (growing from 0.02 to 0.1mm), with granulosa and thecal cells
developing around it (now 0.3mm)
o Follicle swells with fluid (2mm), and receptors for FSH make it dependent on it for development.
15-20 follicles enlarge each cycle, but only one becomes dominant, develops LH receptors, and will
o The follicle is secreting estrogen. This causes a surge in LH starting 36 hours before ovulation.
o Pre-ovulatory follicle stops secreting estrogen and starts secreting progesterone due to LH
o Estrogen also stimulates endometrium proliferation, thickening, and formation of glands that
would secrete substances to nourish the embryo.
o Cervical mucus changes to become spermatozoa friendly for fertilization after ovulation
• 2) Ovulation:
o Pre-ovulatory follicle has enlarged to 25mm. Follicle ruptures to release the mature ovum
o Ovum swept by fimbriae of fallopian tubes, and travels to the ampula in under 24 hours
• 3) Luteal Phase (14 days long):
o Either the ovum was fertilized, or it was not. If unfertilized, the ovum dies; however, the default
system assumes pregnancy and continues preparing for it. If fertilized, hCG produced by
conceptus keeps the corpus luteum intact – cycle length indicates time needed for hcG level to be
o The follicle turns into the corpus luteum, which secretes ↑progesterone. This inhibits ↓LH, and
as LH declines the corpus luteum eventually degenerates. Corpus luteum produces estrogen and
progesterone for 10-12 days.
o There is a sharp ↓estrogen and progesterone, which removes negative feedback – pituitary
begins production of FSH to start the cycle again
o Progesterone stimulates glands of endometrium to start secreting nourishing substances. The
cervical mucus also thickens, making it harder for sperm to penetrate
o The luteal phase is hardest for sperm to transport, but best conditions for a fertilized egg
• 4) Menstruation: The endometrium uterine lining is shed triggered by low estrogen and progesterone;
rising FSH in preparation of follicular phase of next cycle. Page 98-107, 118-123, 16 pages Page 3 of13
• The menstrual fluid consists of blood, degenerated cells, and mucus from the cervix and vagina; total
discharge is about 60mL or 4 tablespoons.
Length and Timing of the Cycle
• Cycles generally last anywhere from 20-36 days, with average of 28 days.
• Day 1-5: Menstruation; 6-13: Follicular; 14: Ovulation; 15-28: Luteal
• Length of luteal phase is relatively constant, with time from ovulation to menstruation about 14 days. In
a 28-day cycle, luteal phase is from day 15-28; in a 44-day cycle, ovulation on day 30 and luteal 31-44.
• Mittelschmerz (middle pain): Some women report they can feel themselves ovulate in a cramping
• Menstruation can take place without ovulation in an anovulatory cycle.
Other Cyclic Changes
• Cervical Mucus Cycle: Glands in the cervix secrete mucus throughout the menstrual cycle, to protect
against bacteria. The glands respond to levels of estrogen.
• At start of new cycle, mucus
is alkaline, thick and viscous.
With increase in LH just before
ovulation, mucus becomes
more thin and watery to enable
sperm passage; a sample
allowed to dry will take on a
fern-shaped patterning (fern
test). After ovulation, returns to
viscous, less alkaline state.
• Basal Body Temperature:
Low temperature in follicular
phase with lowest on day of
ovulation; after ovulation it
rises by 0.3°C or more and
maintains this for rest of cycle.
This is due to increased
progesterone. Basal body
temperature can be used to
determine ovulation for fertility
planning or birth control.
• Dysmenorrhea: Painful
menstruation with cramping
pains in pelvis, headaches,
nausea, bloating, etc.
• This is caused by
prostaglandins produced in
the uterine lining. It causes
smooth muscle contraction in
the uterus (necessary to shed endometrium); interferes with vascularization, and increases sensitivity of
• NSAIDs like ibuprofen are best treatment.
• Masturbation may also be a remedy, as sexual arousal and orgasm decrease pelvic edema, which
contributes to discomfort, pressure, and bloating. Page 98-107, 118-123, 16 pages Page 4 of 13
• Endometriosis: Condition in which endometrium grows abnormally outside uterus, such as fallopian
tubes, vagina, cervix, or bladder. This causes very painful periods with excessive bleeding, pain during
sexual activity, and even infertility of left untreated.
• Amenorrhea: Absence of menstruation. Primary if a girl has not yet menstruated by age 18, and
secondary if she has had at least one period. Causes include pregnancy, congenital defects of
reproductive system, hormone imbalance, cysts or tumours, stress, strenuous exercise, and anorexia
PRENATAL SEXUAL DIFFERENTIATION
• XX for female, XY male; the Y chromosome is smaller and has fewer genes – 80 compared to 1090
• At 28 days after conception, male and female embryos are identical in an undifferentiated state.
However, there are basic structures that will eventually become either a male or female reproductive
• This includes 2 gonads (each with a cortex and medulla), 2 sets of ducts (Müllerian and Wolffian ducts),
and rudimentary external genitals (genital tubercle, urethral folds, genital swelling)
• In the 7 week, sex chromosomes direct the gonads to begin differentiation; the testes start developing
at 7 weeks, while the ovaries develop at 10-11 weeks
• Sex-Determining Region, Y Chromosome (SRY): A gene on the Y chromosome that causes testes
differentiation. It acts on the bipotential genital ridges, bilateral clusters of tissues that develop into
• If present, it leads to production of testis-determining factor (TDF), which causes the genital ridge to
develop into testes. If TDF is not present, female ovary development occurs (the “default” option).
Prenatal Hormones & the Genitals
• 4-5 weeks: Anogenital region consists of cloaca, common exit of GI and urogenital systems.
• Once the ovaries and testes have differentiated, they begin to produce sex hormones that direct the
differentiation of the rest of the system. By 12 weeks, the sex of the fetus is clear from external genitals.
• Genital folds, swelling, and tubercle have androgen receptors for testosterone, then use 5-alpha-
reductase to convert testosterone into the more potent 5-alpha-dihydrotestosterone (DHT) which
masculinizes the external genitalia
• At least 6 genes are involved in prenatal sexual differentiation; a mutation in any one can cause an
Homologous Embryonic Adult Male Adult Female
Gonad (medulla and cortex) Testes (medulla) Ovaries (cortex)
Wolffian Duct Epididymis, vas deferens, Degenerates due to lack of
ejaculatory duct testosterone
Müllerian Duct Degenerates due to Mullerian- Fallopian tubes, uterus, upper part of
inhibiting substance (MIS) vagina
Genital Tubercle Glans of penis Clitoris
Genital Folds Shaft of penis Inner lips, outer third of vagina
Genital Swelling Scrotum Outer lips
Urethral primordia Prostate, Cowper’s glands Skene’s glands, Bartholin glands Page 98-107, 118-123, 16 pages Page 5 of13
Descent of the Testes and Ovaries
• The ovaries and testes start near the top of the abdominal cavity. By the 10 week, they have grown
and moved down to the upper edge of the pelvis.
• The ovaries remain there until after birth, and later shift into adult uterus position in the pelvis.
• The testes descend into the scrotum via the inguinal canal, typically 7 months after conception; on its
descent, the testes pull the vas deferens, blood vessels, and nerves down with it.
• Cryptorchidism is condition of undescended testes by time of birth, occurring in 2% of males;
associated with lower fertility, increased risk of testicular cancer
• In most of these cases, the testes do descend by puberty. However, if this does not occur
spontaneously, surgery or hormonal therapy should be performed before age 5 – if both fail to descend,
the man will be sterile.
• The inguinal canal typically closes after the testes descend; if this does not occur, it may create a
passageway for loops of the intestine to enter the scrotum in inguinal hernia.
• The primary sex-differentiated structure is the hypothalamus, particularly the preoptic area.
• This determines the estrogen-sensitivity of certain hypothalamic cells. If testosterone is present, cells
will become insensitive and not have nucleic estrogen receptors (will have androgen receptors). If
estrogen is present, cells will become highly sensitive to estrogen, crucial to the hypothalamic-pituitary-
gonad feedback loop.
• MRI studies have found a larger volume of hypothalamus and amygdala in men than women; other
regions with few estrogen and androgen receptors do not show these gender differences.
• Neuroscientists reject the notion of “hard-wired” differences present from birth, emphasizing plasticity of
brain in response to experiences
• Homologous Organs: Organs in the male and female that develop from the same embryonic tissue
• Analogous Organs: Organs in the male and female that have similar functions; testes and ovaries are
both homologous and analogous. Page 98-107, 118-123, 16 pages Page 6 of 13
Intersex Conditions: Atypical Prenatal Gender Differentiation
• It is a wrong assumption that if a person is female, she will have feminine traits, identify as a woman, be
sexually attracted to men, have a complete female reproductive system, and the sex chromosomes XX;
same for males.
• There are 8 variables of gender, 6 of them being biological and 2 being psychological
o 1) Chromosomal Gender: XX in female, XY in the male
o 2) Gonadal Gender: Ovaries in the female, testes in the male
o 3a) Prenatal Hormone Gender: Testosterone and MIS in the male, but not female, before birth
o 3b) Prenatal and Neonatal Brain Differentiation: Testosterone present for masculinization of
brain, absent for feminization
o 4) Internal Organs: Fallopian tubes, uterus, and upper vagina in the female; prostate, vas, and
seminal vesicles in the male
o 5) External Genital Appearance: Clitoris, inner and outer lips, and vaginal opening in the
female; penis and scrotum in the male
o 6) Pubertal Hormonal Gender: At puberty, estrogen and progesterone in the female;
testosterone in male
o 7) Assigned Gender: Announcement of girl or boy at birth based on appearance of the external
genitals; gender parents and the rest of society believe the child to be; gender in which the child is
o 8) Gender Identity: The person’s private, internal sense of maleness or femaleness
• As a result of various factors during prenatal sexual development, gender indicated by one or more of
these variables may disagree with gender indicated by others.
• When contradictions are between biological variables, person is said to have an intersex condition, or
a disorder of sexual development (DSD). This biological gender ambiguity is present in about 1-2% of
• Individuals whose assigned gender does not match their gender identity (psychological contradiction)
are considered transgender.
• Turner Syndrome (XO): 1/4000 births. Appear female at birth due to absence of Y chromosome to
• Infertile without complete reproductive system development, lowered levels of estrogen and
progesterone (require medical assistance for puberty), but can experience menstruation and sustain a
pregnancy with use of assisted reproductive techniques
• Short stature, cardiovascular problems, neck webbing
• Klinefelter Syndrome (XXX or XXXY): 1/1000 births. Appear male due to presence of Y chromosome.
• Reproductive problems include low testosterone, low sperm count, and low sex drive. Might also have a
feminine body shape, sparse body hair, and some breast development.
• XYY Syndrome: 1/1500 births, appear male. Genital anomalies, low fertility, and lowered IQ.
• Congenital Adrenal Hyperplasia (CAH): 1/16,000 births
• Problems in producing corticosteroid hormones due to adrenal gland abnormality from recessive
genetic condition, usually associated with stress and immune response; however, they originate from
same precursor as androgens. Overproduction of corticosteroids lead to conversion to higher
concentrations of androgens.
• A genetic female produces abnormal levels of testosterone prenatally, Wolffian duct system may not
degenerate, and therefore has male-appearing external genitals at birth. The labia may partly or totally
fuse with no vaginal opening (appears like scrotum), and the clitoris is enlarged. Page 98-107, 118-123, 16 pages Page 7 of13
• Genetic female individuals with CAH tend to have a female gender identity, tend toward male-
stereotyped toys, and generally function as well as non-intersex women.
• XY individuals are not really affected by CAH in prenatal development, but may experience early
• Androgen Insensitivity Syndrome (AIS): May be complete or partial AIS, 1/10,000 births; on X
• A genetic male produces normal levels of testosterone, but lack functional androgen receptors. Prenatal
internal development is feminized (Wolffian duct regresses w/o testosterone, but anti-Mullerian hormone
still produced by testes), with female-appearing external genitalia and undescended testes (SRY still
produced by Y chromosome, promotes testes development)
• Diagnosed at puberty since female-appearing individual does not begin menstruation
• Infertile, with undescended testes removed. Shallow vagina since Mullerian duct did not develop.
• XX individuals are not really affected by AIS due to diminished role of testosterone in development
• 5-Alpha Reductase Syndrome: 5-a-reductase is enzyme needed to convert testosterone into 5-
dihydrotestosterone (DHT). Does not really affect XX individuals since DHT is not needed anyway.
• Genetic males without DHT, external genitalia will not masculinize. They are born with vaginal pouch
and a clitoris-sized penis, with testes left in labia structures or inguinal canal.
• They would be reared as females, but at puberty would experience surge in testosterone: testes will
descend, clitoris will enlarge to a penis. Most also change gender identity to male.
• Guevodoces (“testicles at 12”) with this disorder first studied in the Dominican Republic are considered
the third gender in their society.
• Micropenis: Unusually small penis <2cm in newborn male. May be caused by hypospadias, the
abnormal location of the urethra on the underside of the glans or shaft, instead of at the tip. Penis growth
can be induced with testosterone treatments or surgeries, but sometimes these individuals are
reassigned as female.
Treatment for Intersex Conditions
• Surgeries or procedures may be performed to normalize genitalia for easier classification as male or
• In CAH girls, the clitoris size may be reduced surgically. Sex reassignment surgery: “easier to make a
hole, than a pole” – more invasive procedure, more tissue required to make a phallus than a neo-vagina
• Physical Outcomes: De