This document discusses reproductive hormones and their functions. It begins by listing the major endocrine glands and the hormones they produce, including the hypothalamus, pituitary gland, adrenal glands, thyroid gland, pancreas, ovaries, and testes. It then discusses steroid hormones in more detail, describing their basic structures. The rest of the document focuses on estrogen, including its synthesis in the ovaries, metabolism, mechanisms of action, effects on various body systems, common pharmaceutical preparations, clinical uses, and potential side effects.

1. Reproductive Hormones
PRO. M.C. BANSAL
M.B.B.S , M.S. , M.I.C.O.G, F.I.C.O.G.
Founder Principal& Controller;
Jhalawar Medical College and Hospital , Jhalawar.
Ex. Principal & Controller;
Mahatma Gandhi Medical college And Hospital,
Sitapura, Jaipur.

2. Location of
Endocrine Glands
In BoDy
Testes
in Males

4. Hormones
1.Hypothalamus-----GnRH.
2. Pituitary –Anterior--- Growth Hormones , FSH ,LH
,Prolactine, ACTH , TSH, Melanin.
---Posterior Pituitatry---ADH , Oxytocin, Inhibin.
3.Adrenals---Mineralocorticoids, Glucocortecoids , androgens
and precursors of female sex Hormones.
4.Thyroid----T3 and T4.
5. Par thyroid—Paratharmone , calcitonin
6.Beta Langer Hans cells(Pancrease)---Insulin.
Alpha cell---Glucagon.
7. Ovary--- Estrogen , progesterone.
8. Testes---- Testosterone.

5. Steroid Hormones
• All steroid hormones are of basically similar structure
with relatively minor chemical differences leading to
striking alterations in biochemical activity.
• The basic structure is the perhydrocyclopenta -
nephenanthrene molecule.
• The sex steroids are divided into 3 main groups
according to the number of carbon atoms they possess.
(A)The 21-carbon series includes the corticoids and the
progestins, and the basic structure is the pregnane
nucleus.
(B)The 19-carbon series includes all the androgens and is
based on the androstane nucleus.
(C) The estrogens are 18-carbon steroids based on the
estrane nucleus.

7. structural formula of steroids 27 ,21 ,19 and 18 C arbon compounds

9. STEROIDOGENEIS
• Cholesterol is the basic building block in steroidogenesis.
• All steroid-producing organs except the placenta can synthesize
cholesterol from acetate.
• Progestins, androgens, and estrogens, therefore, can be synthesized
in situ in the various ovarian tissue compartments from the 2-
carbon acetate molecule via cholesterol as the common steroid
precursor.
• During steroidogenesis, the number of carbon atoms in cholesterol
or any other steroid molecule can be reduced but never increased.
The following reactions can take place:
1) Cleavage of a side chain (desmolase reaction).
2) Conversion of hydroxyl groups into ketones .
3) Conversion of ketones into hydroxyl groups (dehydrogenase
reactions).
4) Addition of OH group (hydroxylation reaction).
5) Creation of double bonds (removal of hydrogen).
6) Addition of hydrogen to reduce double bonds (saturation).

10. The Two Cell System

11. Two Cell
System Of
Ovarian Sex
Steroid
Production

12. Digramatic ----------Grannulosa cells
From Theca cells

16. Blood Transport of Steroids: -- 99% by( SHBG)In
bond Form
• While circulating in the blood, a majority (70%) of the
principal sex steroids, estradiol and testosterone, is bound to
a protein carrier, known as sex hormone-binding globulin
(SHBG) produced in the liver.
• Another 30% is loosely bound to albumin, leaving only about
1% unbound and free ; THE ACTIVE FORM .
• A very small percentage also binds to corticosteroid-binding
globulin.
• Hyperthyroidism, pregnancy, and exogenous estrogen
administration / endogenous production of estrogen --all
increase SHBG levels.
• Corticoids, androgens, progestins, growth hormone, insulin,
and Insulin like Growth factor 1 (IGF-1) decrease SHBG.

18. Hormone

19. Excretion of Steroids:
• Active steroids and metabolites are excreted as sulfo
and glucuro conjugates.
• Conjugation of a steroid converts a hydrophoboic
compound into a hydrophilic one and generally reduces
or eliminates the activity of a steroid.
• Estrogen conjugates can have biologic activity, and it is
known that sulfated conjugates are actively secreted
and may serve as precursors, present in the circulation
in relatively high concentrations because of binding to
serum proteins.
• Ordinarily, however, conjugation by liver and
intestinal mucosa is a step in deactivation preliminary
to, and essential for, excretion into urine and bile.

21. excretion
of
steroids
in
conjugate
form
Either as
Glucosidu
-ronate /
Sulphate

22. Cellular Mechanism of Action:
• Hormones circulate in extremely low concentrations and, in
order to respond with specific and effective actions, target
cells require the presence of special mechanisms.
• There are two major types of hormone action at target
tissues.
• One mediates the action of tropic hormones (peptide and
glycoprotein hormones) with receptors at the cell
membrane level.
• In contrast, the smaller steroid hormones enter cells
readily, and the basic mechanism of action involves specific
receptor molecules within the cells.
• It is the affinity, specificity, and activity of the receptors
present on cell membrane of target cell, together with the
large concentration of receptors inside the cell itself, that
allow a small amount of hormone to produce a biologic
response.

23. Receptors
The many different types of receptors can be organized into the
following basic categories:
Intracellular Receptors
• Receptors in the nucleus of target cell lead to transcription
activation.
• Examples include the receptors for estrogen and thyroid
hormones.
G Protein Receptors
• These receptors are composed of a single polypeptide chain
that spans the cell membrane.
• Binding to a specific hormone leads to interaction with G
proteins that, in turn, activate second messengers.
• Examples include receptors for tropic hormones,
prostaglandins, light, and odors.
• The second messengers include the adenylate cyclase
enzyme, the phospholipase system, and calcium ion changes.

25. Ion Gate Channels
• These cell surface receptors are composed of multiple units,
that after binding, open ion channels.
• The influx of ions changes the electrical activity of the cells.
• The best example of this type is the acetylcholine receptor.
Receptors with Intrinsic Enzyme Activity
• These transmembrane receptors have an intracellular
component with tyrosine or serine kinase activity.
• Binding leads to receptor autophosphorylation and activity.
Examples include the receptors for insulin and growth factors
(tyrosine kinase) and the receptors for activin and inhibin
(serine kinase).
Other Receptors
• Receptors that do not fit the above categories include the
receptors for LDL, prolactin, growth hormone, and some of
the growth factors.

27. Mechanism of Action for Steroid Hormones:
• The specificity of the reaction of tissues to sex steroid
hormones is due to the presence of intracellular receptor
proteins.
• Different types of tissues, such as liver, kidney, and uterus,
respond in a similar manner.
• The mechanism includes:
(1) steroid hormone diffusion across the cell membrane
(2) steroid hormone binding to receptor protein
(3) interaction of a hormone-receptor complex with nuclear DNA
(4) synthesis of messenger RNA (mRNA)
(5) transport of the mRNA to the ribosomes
(6) protein synthesis in the cytoplasm that results in specific
cellular activity.

28. • The steroid hormone receptors primarily affect
gene transcription, but also regulate post
transcriptional events and non genomic events.
Steroid receptors regulate gene transcription
through multiple mechanisms, not all of which
require direct interactions with DNA.

29. Digramatic Illustration of Structure of receptors.l

30. H= Hormone , R= Receptor
HOW
the
steroid
Hormone
enters
Target
cells

35. Intra cellular hormone receptor activity

36. Role of Growth Factor in Hormone synthesis

37. Transcription Activity

41. Estrogen

42. Primary site of Estrogen and progesterone production

47. estrogen
synthesis
in ovary

48. Inter relation ship of E1 , E2 & E3 ( Estrogens)
E3 E2
E1

49. E1– ESTRIOL
E2—ESRADIOL
E3--ESTRONE

51. Estrogen Metabolism(Production)
• Androgens are the common precursors of estrogens.
• 17a-Hydroxysteroid dehydrogenase activity converts androstenedione
to testosterone, which is not a major secretory product of the normal
ovary.
• It is rapidly demethylated at the C-19 position and aromatized to
estradiol, the major estrogen secreted by the human ovary.
• Estradiol is also produced to a major degree from androstenedione via
estrone.
• Estrone itself is also secreted in significant amount by ovaries.
• Thus estradiol and estron are only two varieties of E Hormones
secreted by ovary.
• Estriol is produced by the peripheral metabolite of estrone and
estradiol and not a secretory product of the ovary.
• The formation of estriol is an example of typical general metabolic
detoxification and conversion of biologically active material to less
active forms.
• This mechanism of peripheral production of estriol ( aromatization in
fatty tissue) is the only source of estrogen in menopausal women.

52. Adrenal Cortex ---- Major source of Androstendione– the precurssore for E3 synthesis
• The conversion of steroids in peripheral tissues is not always a
form of inactivation.
• Free androgens produced by ovarian stroma/ adrenals are
peripherally converted in to free estrogens, for example, in
skin and adipose cells.
• The location of the adipose cells influences their activity ,
women with central obesity (the abdominal area) produce
more peripheral conversion of androgens into estriol (E3).
• Enough estriol(E3) may be derived from adipose tissue
sufficient to produce bleeding in the postmenopausal
woman.
• In female the adrenal gland remains the major source of
circulating androgens particularly as Androstenedione.
• In male, almost all of the circulating estrogens (though
minimal) is derived from peripheral conversion of androgens
but it is not sufficient to cause feminization.

55. Pharmacological Action Of Estrogen
1) Sex organs: The estrogens bring about pubertal growth spurt--
development of secondary sex characters and changes in the female
including---
development of breast , growth of uterus, fallopian tubes and vagina.
Suppresses FSH and LH secretion , stimulates LH surge,
• Vaginal epithelium gets thickened, stratified and cornified, intracellular
Glycogen deposition---lacto bacilli produce lactic acid--- Vaginal Ph --
acidic.
• They are responsible for the proliferation of endometrium in the pre
ovulatory phase and it is only in concert with estrogens that progesterone
brings about secretory changes.
• Estrogens increase rhythmic contractions - the fallopian tubes and uterus,
• Induces watery alkaline secretion from the cervix favorable to sperm
penetration.
• They also sensitize-- the uterus to oxytocin and PGs.
• Deficiency of estrogen is responsible for atrophic changes in the female
reproductive tract that occur after menopause

56. Pharmacological Action of Estrogen---
2) Secondary sex characters:
• Estrogens induces( at puberty) growth of breasts, proliferation of ducts
and stroma and fat deposition in breast.
• Growth of pubic and axillary hair., though the sex hair growth is initiated
by androgens( derived from Adrenals) to start with.
• Feminine contours and behavior.
3) Metabolic effects:
• Estrogens are anabolic, similar to but weaker than testosterone.
• Effect on carbohydrate , protein and lipid metabolism---Increases fasting blood
sugar level , increase serum hormone binding protein , Increase in HDL and
decrease in LDL
• Estrogen is important in maintaining bone mass primarily by retarding bone
reabsorption. , its declined level in menopause is responsible for menopausal
osteoporosis.
• It promotes positive calcium balance, partly by inducing renal hydroxylase enzyme
which generates active form of Vit D,
• Pharmacological doses of estrogens can result in mild salt and water retention---
edema may develop.
• BP may rise after prolonged use.
• it is cardio protective in normal physiological dose.
• Increase in coagulation factors and Fibrinolysis.

58. Pharmacological Action of Estrogen--------
• Estrogens decrease plasma LDL cholesterol while HDL and
triglyceride levels are raised.
• The raised HDL : LDL ratio is probably responsible for rarity of
atherosclerosis in premenopausal women.
• However, blood coagulability is increased due to induction of
synthesis of clotting factors (factors II, VII, IX and X).
• Fibrinolytic activity in plasma also tends to increase.
• Estrogen increase Lithogenecity of bile by increasing
cholesterol secretion and reducing bile secretion.
• Estrogen increases Plasma levels of sex hormone binding
globulin (SHBG), thyroxine binding globulin (TBG) and cortisol
binding globulin (CBG) -----but without any change in active
form of hormonal status

59. Estrogen effect Estrogen&
Progesterone
E & P
withdrawl

63. Ovarian aging and anovulation , decreased No . Of follicle ----decreased Estrogen
Production Hence FSH level rises abruptly in menopausal and andropause age

64. Preparation And Doses of Estrogen -------Table1
Oral Preparations Doses
Ethy-inyl estradiole (Lynerol ) 0.01 ,o.03 . 0.05 , 0.1 mg daily
Conjugated equine estrogen
(premarine , conjugase )
0.3 .0.625 .1.25 mg daily.
Estrified Estrogen( Estratab ) 0.3 . 0.625 mg daily.
Micronised Estrogen (Estrace) 1-2 mg daily.
Trans dermal---
Estradiol Patches (E straderm)
Estradiol Gel ( (Estrogel)
0.025, 0.05 mg twice a day
1.25 mg daily
Intramuscular preparations –
Estradiol Velerate(Delestrogen )
Estradiol cypionate (depo-estrogen)
10,20mg once in 4 weeks
1.5-2mg once in 4 weeks.

65. Estrogen Preparations ------ ---Table2
Intravenous—
Conjugated equine estrogen (
Premarin)
25mg 6 hourly .
vaginal Preparations---
1. Estradiol Creams(Estrace )
2.Conjugate estrogen
Creams(Premarin)
3. Estradiole vaginal ring (Estring)
4.Estradiole vaginal (Vagifem )
0.01% daily .
0.025 . -2mg / day
1ring once in 3 months.
1 tablet daily .
EstradioleImplant 25 ,50, 100mg once in 3 months.

66. Clinical Uses Of Estrogens--------
In combined Oral Contraceptives (OCS) Ethinyl estradiole / Mestranol .
Post Menopausal Hormone Therapy. Conjugated Estrogen ,implant , patch .
For Development Of secondary Sex
Characters –
Turners Syndrome.
Hypogonadotrophic – hypogonadism.
Partial Androgen insensitivity
Ethenyl estradiole 0.1mg / day
continuously for 3-6 months than
maintenance therapy—0.01 mg / day
cyclically for 21 days .
FUB— Ethanol Estradiole / Iv conjugate 25mg
6hrly till bleeding controlled followed by
ocs /ocs only
Vulvovaginitis in Children Vaginal Cream
Post menopausal vaginal atrophy /
cystitis
Vaginal cream, gel . Ring . Tablet

68. Side Effects of Estrogen Therapy
• Nausea and Vomiting.
• Breast Tenderness.---Increases incidence of ER +Ve carcinoma of
breast in female with heredo familial predisposition.
• Migraine.
• Thrombo embolism .
• Endometrial carcinoma –with prolonged unopposed use.
• Gallbladder disease.
• Stroke .
• DVT.
• Hepatic Adenoma.
• Intra Hepatic Choleastesis.---Jaundice.
• Water and electrolyte pretension.
• Worsens Hypertension.

70. Selective Estrogen Receptor Modulators(SERMS)
• There are 2 types of estrogen receptors—
1. ER a
2 . ER b
Drugs which bind to or modify a particular type
of receptor have abroad spectrum of action ---
estrogenic / antiestrogen on different tissues.
SERMS--- are non steroidal drugs – have estrogenic
action on bone, brain , liver But antiestrogenic
action on breast and endometrium .

71. Currently Available SERMS
Drug Usual Dose Indication Estrogenic effect on Anti estrogenic
effect on
Contra Indication
Temoxifen 10-20 mg / day
Breast cancer
,Gynaecomastia , Hot
flushes.
Liver, endometrium –
increased risk of Ca
.Endo. bone(inhibits
osteoclasts –prevent
osteoporosis, brain
Breast .---Prevent
recurrence of ca
breast .Decrease ca
by 50 %in contra
lateral breast, % yrs
therapy increases
disease free survival
women with uterus
–need follow up by
TVs and End
Sampling. And not to
give when high risk
factor for Ca,. Endo.
+Ve
Reloxifene. 60 mg / day Postmenopausal
osteoporosis, Breast
Cancer
BONE– post
menopausal
osteoporosis
prevented
Breast-ER+ve cases
of Ca breast are
benefitted-
Ormeloxifene—
(centochrome ,
Saheli,Seviesta)
Azoxifene
30-60mg , 60 mg
tab--2 tabs state –
1 tab bi weekly for
DUB.
20mg
DUB ,
Contraception( 30mg
twice a week for 3
months then once a
week )
Breast cancer
It cause asynchrony
between ovulation
andendomatrum ---
preventing
conception.
Present

74. Anti Estrogens
• Unlike SERMS ( having estrogenic / anti
estrogenic effect on different tissue ) These
drugs have only anti estrogenic effect on all
the tissue where ever estroge4n receptors are
present.
• Two main drugs belong to this category ---
1. Clomiphene Citrate.
2. Fulvestrant .

75. 1.Clomiphene Citrate
• Clomiphine inhibits Negative feedback inhibition of GnRh
done by indigenous estrogen --- it results in increased
secretion of GnRH ---FSH secretion, LH surge and induces
ovulation .
• It is prescribed in dose of 50 – 150 mg / day since 2nd day
to 6th day after LMP., the period of time when Estrogen is
rising and a crop of Follicles are in race of development and
selection of dominant follicle occurs in ovary.
• Clomiphene binds to estrogen receptors on hypothalamus
and blocks -ve feed effect of the estrogen on
hypothalamus thus Pulsatile GnRH secretion ensures the
resultant rise in FSH secretion From Pituitary ---- stimulates
ovarian multiple follicles to develop ,Estrogen produce from
these follicles with its +be feed mechanism brings about
ovulation ( multiple)

76. 1.Clomiphene---Suppress -Ve feed mechanism of
Estrogen by blocking Receptors
2.GnRh secretion By
3.FSH secretion &
4. LH Surge By
Anterior Pituitary Ovary
Estrogen.
hypothalamous
Ovary
5.Multiple follicle run in race of Maturation and 1 or
more follicles become dominant follicle to ovulate

77. 1. Clomiphene citrate -----
Clinical Use
Anovulation , PCOD ,Un explained Infertility . Stimulation of
spermatogenesis in males having Azoo / Hypospermia due to
hypogonadotrohin –hypogonadism.
Doses Started in low dose (50mg /day )on day 2for 5 days --- can be
increased gradually up to 150-200 mg / day –Maximum for 6cycles
For induction of ovulation. In male 25mg/ day for 25 days a month
up to 6 months for treatment of Azoo/ hypospermia.
Side effects Hot flushes , blurring of vision and scotoma , abdominal
discomfort , Nausea & vomiting , multiple ovulation --- multiple
pregnancy , Luteal phase defect , Anti estrogenic effect on cervical
mucous and endometrial changes ,Ovarian cysts and cancer (>
1year of use ) and ovarian hyper stimulation syndrome.
2. Fulvestrant---is similar to tomexiphen but having only anti
estrogenic effect on all tissue , it is used in women with breast
cancer (ER+ve) . It is administered as IM depo Preparation

78. Estrogen Synthesis Inhibitors---are Aromatase Inhibitors(AIs)
• Pharmacology conversion of Androgens in to estrogen require
Aromatase enzymes.
• This enzyme is predominantly present in grannulosa cells and peripheral
adipose tissue , liver breast and placenta.
• By inhibiting the action of this –aromatase enzyme biosynthesis of
estrogen can be blocked in vitro as well as in vivo .
Types Of AIs—The are of two types—
1. Type I : Steroidal Agents ( Formestane and Exemastane ). They bind with
aromatase and their binding is irreversible causing permanent blockage of
aromatization –no more estrogen synthesis.
2.Type II : Non steroidal agents(Anastrazole and Latrozole ) The binding
with aromatase is reversible hence short acting blocking effect on
estrogen production occurs.
Clinical Use postmenopausal breast cancer—second lime therapy in
recurrent cases, 1st line as adjuvant ,Preoperative ( neo adjuvant
).Ovulation Induction , endometriosis, Fibroid s. Endometrial stromal
sarcoma, peripheral precaucious puberty , congenital adrenal hyperplasia
,short stature girls--- prevents fusion of epiphysi of long bones ,
Gynaecomastia.

79. Preparations And doses Of Aeromatase
Inhibitors
Preparations Doses
Letrazole 2.5 mg daily
Anastrazole 1 mg daily .
Exemestane ( steroidal agent –
permanent inhibitor ) 25 mg daily
Side Effects of AIs
Arthralgia and arthritis
Dyslipidaema.
Vaginal Dryness.
Coronary heart disease .
Osteoporsis.
osteonecrosis of Jaw.
Note --- Letrazole is not recommended
for induction of ovulation in India as it is
an anti cancer drug . Its use for induction
of ovulation is also not approved by drug
controlling authorities of USA and British
Pharmacopeia.

80. Mechanism Of action of Leterazole---
Ovulation
• Normally Grannulosa cells produce estrogen –Androgens
are converted in Estrogen by the action of Aromatase
Enzyme.
• Laterozole temporarily inhibits aromatase enzyme  No
estrogen production no more – ve feed action of
estrogen on Hypothalamous-->Pulsatile secretion of GnRH
occurs GnRH Stimulates anterior Pituitary FSH
secretion FSH acts on Grannulosa cell--- development of
FSH receptors and Initiates race of development of multiple
follicle to win as dominant follicle .
• By now the inhibitory effect on aromatase enzyme(
Leterozole) wears off-Estrogen production by Grannulosa
cells re start– Rising estrogen level  It further stimulate
anterior pituitary  FSH is produce and LH surge occurs
causing –Ovulation of dominant Follicle.

81. Progestrogens

82. Production of progesterone:
• Progesterone , like all other steroid hormones, is synthesized from
pregnenolone , which in turn is derive from cholesterol.
• Cholesterol undergoes double oxidation to produce 20,22-
dihydroxycholesterol .
• This vicinal diol is then further oxidized with loss of the side chain
starting at position C-22 to produce pregnenolone .
• This reaction is catalyzed by cytochrome P450scc.
• The conversion of pregnenolone to progesterone takes place in two
steps. First, the 3-hydroxyl group is oxidized to a keto group and
second, the double bond is moved to C-4, from C-5 through a
keto/enol tautomerization reaction.
• This reaction is catalyzed by 3beta-hydroxysteroid
dehydrogenase/delta(5)-delta(4)isomerase.
• Progesterone in turn is the precursor of the
mineralocorticoids, aldosterone, and after conversion to 17-
hydroxyprogesterone of cortisol and androstenedione.
• Androstenedione can be converted totestosterone, estrone
and estradiol.

85. Progesterone Metabolism:
• Like E, peripheral conversion of steroids to progesterone is
not seen in the non pregnant female; rather, the progesterone
production rate is a combination of secretion from the
adrenals and the ovaries.
• Including the small contribution from the adrenal, the
production rate of progesterone in the pre ovulatory phase is
less than 1 mg/day.
• During the luteal phase, production increases to 20 to 30
mg/day.
• The metabolic fate of progesterone, as expressed by its many
excretion products, is more complex than estrogen.
• About 10 to 20% of progesterone is excreted as pregnanediol.

87. Metabolism of progesterone

88. • In the pre ovulatory phase in adult females, in all pre
pubertal females, and in the normal male, the blood levels of
progesterone are at the lower limits of immunoassay
sensitivity: less than 1 ng/mL.
• After ovulation, i.e., during the luteal phase blood level
of progesterone ranges from 3 to 15 ng/mL.
• In congenital adrenal hyperplasia, progesterone blood levels
can be as high as 50 times above normal.
• Pregnanetriol is the chief urinary metabolite of 17 alpha
hydroxyprogesterone and has clinical significance in the
adrenogenital syndrome, in which an enzyme defect results in
accumulation of 17 alphahydroxy-progesterone and increased
excretion of pregnanetriol.

89. Digramatic Illustration of Progesterone hormone

90. Pharmacological Action Of Progesterone
• Uterus: The main function of progesterone is preparation of the uterus
for nidation and maintenance of pregnancy due to prevention of
endometrial shedding, decreased uterine motility and inhibition of
immunological rejection of Fetus from pregnant Uterus
(Immunomodulation)
• Progesterone brings about secretory changes in the estrogen primed
endometrium: hyperemia and tortuocity of glands .
• Continued action of progesterone (as when pregnancv occurs) brings
about decidual changes in endometrium- --stromal hyperplasia and it
becomes spongy ,hypervascular , the glands atrophy afterwards.
• It also decreases sensitivity of myometrium to oxytocin and PGs
• Cervix: Progesterone converts the watery cervical secretion induced by
estrogens to viscid, scantv and cellular infiltration which is hostile to
sperm penetration. Fern and straechability in thread( spin Barket)
properties disappear.

91. • Vagina: Progesterone induces pregnancy like changes in the
vaginal mucosa-leukocyte infiltration of cornified epithelium
(KI index decreases e,g More % of navicular cells).
• Breast: Progesterone causes proliferation of acini in the
mammary glands
• Body temperature: It causes a slight (0.5,'C) rise in body
temperature by resetting the hypothalamic thermostat and
increasing heat production.
• Respiration: Progestins in relatively higher doses stimulate
respiration, as occurs during Pregnancy.
• Metabolism: Prolonged use of oral contraceptives impairs
glucose tolerance in some women. This has been ascribed to
the progestational component.
• Progestins, especially those with androgenic activity (19-
nortestosterone derivatives) tend to raise LDL and lower HDL
levels.

92. Thermogenic Effect Of Progesterone at
the time of Ovulation

93. Classification Of Progestins
• Progesterone—Micronized , 17 Alpha Hydroxy
progesterone caporate .
• C 11 – steroid ---Medroxy progesterone acetate , Magestrol
acetate.
• Pregnanes –(17 acetoxyprogesterone deravatives )
Lynestrenol.
• Estranes –(19 –Nor testosterone derivatives )—
Norethsterone, norethinedrol ,Norethydrone, ethynedilol
diacetate.
• Gonanes– Norgestrel ,Levonorgestrel .
• Newer Progestins---Desogestrel ,Gestodene ,Norgestimate .
• Spironolactone Derivatives---Drospirenone .
• Other Progestins ---Dienogest ,Nomegestrol ,Nestorone ,
trimegestone.

94. Preparations and Dosages
Preparations Doses Route of administration
Micronised Progesterone 100-200mg Oral/ vaginal
!7 – alpha Hydroxy –prog.Caporate 250-500mg weekly IM
MPA 2.5-5 mg
150 mg
Oral
IM Depot
Megestrol Acetate 10mg oral
Norethysterone 5mg oral
Norgestrel 5mg oral
Lvonorgestrel
Desogestrel
Gestodene
Drospirenone
Norplant I & II
Implanon
Vaginal Ring
Progestasert
Lenorgestrel (Mirena)
5mg
10 mg
75 ug (withEE2)
3mg (with EE2 )
36mg,70mg
Etonogestrel 67mg
releases 20ug/day
Progesterone—38mg
52 mg
oral
oral
Oral
oral
Sub dermal
Sub dermal
Transvaginal
IUCD
IUCD

95. Clinical Uses Of Progesterone
• Diagnostic ---Progesterone Challenge test 
1omg progesterone / day for 10 days If brings
about with drawl bleeding in a women with
secondary amenorrhea– indicate sufficient
amount of Estrogen is present , endometrial is
able to respond to hormones ,when No with
drawl bleeding occurs– Either there is no
sufficient estrogen production or the endometrial
is not primed (no proliferative changes could
develop) as it is damaged by local disease like
Tuberculosis or Asher Man’s syndrome.

96. Clinical Use of progesterone--Therapeutic
•WithT hEsetrraopgeenutics--- Combined OC pills . Postmenopausal Hormone
therapy
Progestin-only Contraceptives Minipill, Norgestrel . Desogestrel .MPA –depot ,
Implants, IUCD--Mirena
Emergency Contraception Levonorgestrel
DUB Duphaston , Promolut-N , Diavary , Regosterone.
Recurrent Abortions Duphaston , 17 –alpha Hydroxyprogesterone
acetate, micronised progesterone.
Secondary Amenorrhoea with normal / increased
Estrogen
Norethisterone
Lutial phase Defect in ART cycles Micronised Progesterone
Preterm Labour
Endometriosis
Endometrial Hyperplasisa
Advanced endometrial Cancer
Postponement of menses
Micronized Progesterone
Norethisterone, MPA.
MPA , Megetrol acetate.
MPA , Megestrol Acetate.
Nor ethisterone.

97. Side effects of Progesterone Therapy
• Nausea , Vomiting .
• Mastalgia .
• Sodium & water Retention.
• Worsening of Hypertension.
• Depression.
• Dyslipidaemia .
• Thromboembolism .
• Brest cancer –prolog use.
• osteoporosis – Prolong use.
• 19 nor testosterone Der55ivatives – can cause hirsutism---
Virilisation of fetus if given to pregnant women.

98. Antiprogestins
• Antiprogestins act by binding to progsterone receptors and block
the progesterone effect on Target cell.
• Mifepristone--- Derivative of norethisterone.
• When given in Luteal phase ---cause luteolysis—resulting in
menstruation as with drawl bleeding .
• In early Pregnancy –lutolytic effect  decreased Progesterone
levels , decidual breakdown and embryonic demise—Endogenous
production of PGs start myometrial contractions --- Abortion .
• If given in(2oomg oral) late proliferative Phase( 11- 14 Day ) , it
causes Suppression of LH surge --- No Ovulation.
• These drugs also have anti androgenic and anti gluco corticoid
action also and cause rise in ACTH level .
• These drugs are metabolized in liver.
Preparations –
1. Mifepristone
2 . Onapristone
3 .Epostone.

99. Clinical Use of Mifepristone
• Medical termination of early (<49 days / 7 weeks from
LMP) Pregnancy. It is given in 6oomg orally initially,
Adding Mesoprostol 400 ug (oral / vaginal ) after 24-36
hrs gives > 95 % success. Products are expelled within 5
days .
• Post coital pill 1o mg if taken immediate after
intercourse in pre ovulatory phase.
• Also useful in--- cervical ripening , Endometriosis, break
through bleeding IN MPA dept therapy , Leomyoma,
breast cancer (PR +VE ),Ovarian cancer , cushing’s
syndrome and premenstrual psychotic depression etc.
• Side Effects Nausea, vomiting , Uterine Cramps ,
adrenal insufficiency and cardiac Failure.

100. Selective Progesterone Receptor
Modulators (SPRMs)
• SPRMs act on progesterone receptors , the
have stimulating effect (progestogenic ) as
well as Anti progestogenic effect on different
tissue Having different type of PRs.
• Only drug yet developed is ASOPRISINIL.
• It is under trial in cases of endometriosis,
fibroids and breast cancer.

101. Androgens

102. Cerebral
Cortex –
Hypothalmo-
Pituitary
Testicular Axis
in male ---
Androgen
Production
+Ve effect on Male
body( Sexual aswell
as Asexual systems

104. Male Reproductive System _____Androgen production

108. Androgen Metabolism IN Females:
Ovary ---The major androgen products of the ovary are
dehydroepiandrosterone (DHA) and androstenedione (and only a
very little testosterone), which are secreted mainly by stromal
tissue derived from theca cells.
With excessive accumulation of stromal tissue or in the presence
of an androgen-producing tumor, testosterone becomes a
significant secretory product of ovary.
The normal accumulation of stromal tissue at midcycle results in
a rise in circulating levels of androstenedione and testosterone
at the time of ovulation.
Adrenals ---Under normal circumstances, adrenal gland
production of the sex steroids is less significant than gonadal
production of androgens , estrogens and progesterone.
.

109. • About one-half of the daily production of DHA and
androstenedione comes from the adrenal gland; the other
half of androstenedione is secreted by the ovary.
• but 50%of DHA is from theAdrenals;20% from ovary and rest
comes from peripheral tissues.
• The production rate of testosterone in the normal female is
0.2-0.3 mg/day, and approximately 50% arises from peripheral
conversion of androstenedione (and a small amount from
DHA) to testosterone, whereas 25% is secreted by the ovary
and 25% by the adrenal.
• Reduction of the unsaturation (an irreversible pathway) in
testosterone is very significant, producing derivatives very
different in their special configuration and activity.

110. • The 5β-derivatives are not androgenic, and this is not an
important pathway; however, the 5α-derivative (a very active
pathway) is extremely potent. Indeed, dihydrotestosterone
(DHT), the 5α-derivative, is the principal androgenic hormone
in a variety of target tissues and is formed within the target
tissue itself.
• In men, the majority of circulating DHT is derived from
testosterone that enters a target cell and is converted by
means of 5α-reductase to DHT.
• In women, because the production rate of androstenedione is
greater than testosterone, blood DHT is primarily derived
from androstenedione and partly from
dehydroepiandrosterone.
• Thus, in women, the skin production of DHT may be
predominantly influenced by androstenedione.

111. Metabolism of
Testosterone

112. Diagramatic Illustration Of structure of Androgen Receptor

113. androgen receptor-
--Cellular
machenism

114. Pharmacological actions of androgens In Women:
In women, androgens play a key role in the
hormonal cascade that kick-starts puberty,
stimulating hair growth in the pubic and underarm
areas.
Additionally, these hormones are believed to
regulate the function of many organs, including the
reproductive tract, bone, kidneys, liver and muscle.
In adult women, androgens are necessary for
estrogen synthesis and have been shown to play a
key role in the prevention of bone loss, as well as
arousal of sexual desire and satisfaction.
They also regulate body function before, during
and after menopause.

115. Preparations of Androgens
1.Testosterone Esters –
- testosterone enanthate
- testosterone Cypionate.
- testosterone undecanoate.
2. 17 alpha –Alkylated androgens
- Methyl Testosterone
- Oxandrolone
- Fluoxy mestenone
- Danazole
3. 19 N0r Derivatives
- Gestinone.

116. Clinical Use of Danzol
Oral
Endometriosis------600—800mg/day
Fibrocystic Disease of Breast--100 –200mgdaily.
Menorrhagia –200mg /day.
Mastalgia--- 50—100mg/day .
Immune thrombocytic Pupura 200mg/day.
Angoeodema------200mg/day .
Emergency Contrceptive—200mg stat post coital.
Vaginal 
Endometriosis—1500mg

117. Gestinone
Effects
This is a19-Noortestosterone derivatives with
androgenic,antiestrogenic ,antiprogestrogenic , and anti
gonadotrphic action.
• It suppresses LH surge and basal LH secretion from pituitary and
increases free testosterone level .
• It has been used in treatment of Endometriosis and has been found
to be effective as GnRH analogues.
• The recommended dose is 2.5 mg twice a week.
• About 80% of women become amenorrhoeic.
Side effects 
Its effects are similar to Danezol ,but less severe.
Nausea, Muscle cramps , weight gain , Acne, oily skin , Facial hair
growth etc.

118. Anti Androgens
• They are used when androgen levels are high and / or their effect on body are
undesired .
• In women their principal use is in Hirsutism .
• Varieties
1, One who decrease androgen production .
2, One those inhibit the action of androgens on target cell by blocking their
receptors.
Anti androgens
A. Inhibitors of androgen secretions—GnRH analogues, anti fungal like Imidazole
and Ketaconazole.
B. Inhibitors of Androgenic action on target cells—
(a) inhibitors of testosterone action ---Cyproterone Acetate ,Spironolactone,
Flutamide , Bicalutamide ,Nilutamide and Cimetidine .
( b ) 5 alpha Reductase enzyme inhibitors ---Finasteride and Dutasteride.

119. Androgen Receptor Inhibitors
Cyproterone Spironolectone Flutamide
Chemical Nature Synthetic
Progesterone
Aldosterone
antagonist
Substituted anilide
Mechanism of
action
plasma T,A-dione,
SHBG ,anti glco
corticoid
Suppression of T
biosynthesis,
Inhibition of5 alpha
redutase.
anti androgen ,
week inhibitor of T
biosynthesis.
Indiocations Hirsutism , Acne Hirsutism hirsutism
Doses 100mg / day for 5-
15 D with EE2 30ug
/day for 5-26 d of
cycle
50-200mg/ day 250 mg 2-3 time /
day
Side effects Nausea , wt gain ,
headache, fatigue,
irregular menses ,
Teratogenic
Irregular menses,
Mastalgia,
urticaria,hair loss
,Hyperkalaemia,
Feminization of
fetus,Teratogenic
Dry skin, Blue green
discolouration of
urine
.Hepatotoxicity ,
Teratogen

120. 5 alpha Reductase inhibitors
• Finestride
It is a specific inhibitor of 5 reeducates enzyme which
converts Testosterone into the more potent androgen ,
Dihydrotestosterone.
Used in 1.Rx of benign hyperplasia of Prostate.
2. Hirsutism along withjcombined Ocs.
3. also useful in females with male type
baldness.
Indications—Hirsutism and male type of baldness in
females.
Side effects --- Hypersensitivity ,Teratogenicity .
Dose– 5-10mg/day

121. Neuro endocrinology in female
steroid Hormones production and
regulation

123. Neuro transmitters
• The most important neurotransmitters in reproductive neuro
endocrinology are the three MONO AMINES--- Dopamines,
Norepinephrine and Serotinins.
• Dopamoine containing fibers that regulate pituitary function arise chiefly
in hythalmic—arcuate nucleus ; these fibers project to median eminence
where Dopamine enters the portal vessels of hypothalmo –hypophysial
system .
• Dopamine present in small amount in portal system is sufficient to inhibit
the release of Prolactin (PRL).
• Dopamine is most potent and important PRL inhibiting Factor (PIF).
• Pulsatle and phasic Inhibtion of prolactin release in pulsatle manner is
principally responsible for pulsatile secretion of GnRH --- in turn secretion
of Gonadotrophins (FSH and LH ) in phasic stages of normal menstrual
cycle.
• Endogenous prolactin releasing substances like TSH ,Vasopressin ,
Vasoactive Intestinal peptides (VIP) , opoids and acetyline.
• There are 5 types of dopamine receptors groped in D1 & D2 sp[ecific
ligends. Anterior Pituitary primarily express D2 type of specific ligends.
• Opoids tone in brain plays acentral role in menstrual cyclicity by
suppressing GnRh release.

124. Hypothalmo—pituityary Axis

126. Neuro – Vascular relation in Hypopthalmus and pituitary

136. Hypotyhalmo
- Pituitary-
Ovarian Axis -
--Regulation
of Sex steroid
Production
By Ovary In
Females
GnRH
releasing
Hormone
FSH &
LH
Estrogen
&
Progester
one
-Ve And +Ve
Feed
machanism
Regulate the
Production Of
E & P
hormones

143. Neuro-Endocrinological regulation of Sex Steroid Production From Gonads

144. Gonadotrophin Releasing Hormone
• Gonadotrophin releasing hormone is deca peptide, release
in a pulsatile fashion by the hypothalamus.
• This pulsatile pattern is crucial for synthesis and secretion
of Gonadotrophins ---FSH and LH etc.
• Continuation administration of GnRH hormones/Their
synthetic analogues. lead to transient increased levels of
FSH and LH ( flare up effect )– then it is followed by prolong
desensitization of GnRH receptors present on pituitary cells
--- resulting prolong inhibition of FSH and LH secretion (
down Regulations ).
• This is the basis of use GnRH analogues in clinical practice.
• Half life of GnRH is only 2-4 minutes hence GnRh analogues
with enhanced potency and duration of action have been
synthesized.
• They are in activated by gastric juice hence the are given
parentally.

146. GnRH Analogues preparations
Preparation Doses Route of
administration
Bucklin 300ug IN / Sc IN, SC
Naferelin 400ug IN daily In ( Intra Nasal )
Goserelin 3.6mg implait 3
monthly
3.6mg monthly
Sc implant ( Sub
Cutaneous)
IM Depot
Leuprolide 3.75 mg IM
monthly
IM ,SC, DEPOT

147. Diagnostic use of GnRH Analogues
• Stimulation of hypothalmus with GnRh analogues
( gonadorelin ) results in3-4 fold rise in FSH and
LH levels in a women having Hypothalamic
amenorrhea (hypothalamic Failure ). If it is due to
pituitary failure --- No such response ( no rise in
FSH& LH secretion).
• In central precocious puberty , basal FSH and LH
levels are in the range of post pubertal range;
Groh analogues administration will result in 3-4
fold rise in their serum level indicating that
hypothalamus-pituitary ovarian axis is
synchronized and active . In peripheral is sexual
precocious puberty , FSH & LH levels are low and
there is no increase after Groh stimulation.

148. Clinical Indication Of GnRH Analogues
• Pulsatile administration  Hypothalamic amenorrhea,
Infertility , Down regulation prior to ovulation Induction ,
ovulation induction in hypothalamic dysfunction.
• Daily or monthly administration Central precocious
puberty , endometriosis , Uterine myomas to reduce their
size ( preoperatively ),
DUB ., Endometrial preparation for TCRE.
Hormone responsive breast carcinoma, cryptorchidism and
prostatic cancer in males.
Side effects Hot Flushes , Vaginal dryness ,insomnia
,dyslipidaemia , osteoporosis.
Add Back Therapy  due to side effects ,GnRH therapy is
usually limited to 6 months. If treatment is to be given for
long duration Add back therapy with combined oral pills /
or estrogen alone is given . When estrogen is contra
indicated Tibolone may be considered.

149. GnRH Antagonists
• GnRh antagonist act Blocking GnRh receptors
on pituitary , faster in action, no initial GnRH
flare up and used for rapid down
regulationprior to ovulation in ART.
• Preparations available
Cetrorelix, genirelix and aberalix use d as
sub cutaneous injection. Not commomnly
used because of their hypersensitivity
reaction.

150. Gonadotrophins --- FSH and LH
• FSH stimulates follicular growth, and production
of estrogen by grannulosa cells in ovary .
• LH surge (+ve Feed mechanism of rising estrogen
on pituitary) triggers Ovulation , stimulates
Progesterone production , Sustain the life of
carpus luteum and supports implantation of
fertilized ova in decidual bed .
• Commercially available preparations of FSH & LH
are used for these functions in ART practice.

151. Preparations of GnRH (FSH & LH ) And doses
Hormone Source Brand Name Dose route of
Administration
Menotropin (
equal amount of
FSH and LH)
Extracted from
urine of Pregnant
women
Pergonal
Repronex
75 IU IM
Urofolicotrophin
(u FSH )
Highly purified
Form from urine
of pregnant
women
Bravelle FSH-- 75 IU SC
Recombinat (rFSH )
These are
Expensive and not
used as routine
Synthesized by
DnA recombinant
Technology
Gonal F
Puregon
Follistin .
50 IU SC
Chorionic
Gonadotrophin
Pregnyl
Profesi
Novarel
More LH effect
extracted from
urine of pregnant
women
1000-5000IU IM

152. Clinical uses of FSH and LH preparations
• DiagnostichCG stimulation is used to stimulate
testosterone production from Leydig cells of testes --- thus
detect Leydig cell function . This test is used in children
with ambiguous genitalia – hCG response in the form of rise
in Testosterone level indicates presence of testes/ testicular
component.
• Therapeutic Uses
FSH and LH (hCG)---infertility for induction of ovulation
,Hypogonadotrophic hypogonadism and cryptorchadism.
hCG alone ---Recurrent pregnancy loss and luteal ph
support in IVF .
Side Effects  Multifetal pregnancy , and ovarian hyper
stimulation syndrome (OHSS) in induction of ovulation in
ART.

153. Prolactin

154. Prolactin
• Prolactin is produced by Lactotrophes of (
Insulin like Growth factor) pituitary gland and
has single chain of 198 amino acids; it plays a
vital and major role in preparation of breasts
for lactation and continuous milk secretion .
• Drugs used to inhibit Prolactn (PRL)
Preparation Doses (mg) Route of Administration
Bromoergocryptine 2.5-7.5 Oral/vaginal /day
Cabergoline o.25-o.5 Oral twice weekly
Quinagolide o.1-0.5 Oral / day
Pergolide o.o25-o.5 Oral daily

155. Clinical Use Of Prolactin Inhibitors
• Hyperprolatinaemia.
• Prolactinoma .
• Suppression of Lactation.
• Mastalgia.
• Infertility / amenorrhea due to hyper prolactinaemia.
• Side effects
Nausea,vomiting , headache , postural hypotension ,
nasal congestion ,CNS effect like—insomnia,
hallucinations, psychosis.
These drugs should be starte with smalldose and then
increase gradually at interval of ½ week. Mild side
effects usually subside as time passes.