Contraception/Pregnancy/ reproductive health

16 & 17

Combined oral contraceptives
-Can have oestrogen and progestogen components

•Prevents ovulation
•Thickens cervical mucus
•Thins the endometrium

Oestrogens:
•Almost all contain ethinylestradiol (20-40mcg)

Progestogens:
•˃10 different progestogens

-Monophasic: same amount of oestrogen/progestogen in every tablet
-Phasic: varying amounts of oestrogen/progestogen in different tablets

a common concern among women using hormonal birth control. It's usually a small amount of spotting at a time when you're not expecting your period, though some women have heavier bleeding.

Reserved for:
-Breakthrough bleeding on monophasic preparations
-No bleed on pill free interval

20mcg: Millinette, Gedarel

-Patient with risk factors for VTE (e.g. family history, over 35 years, smoker, obesity, immobility

-levonorgestrel, norgestimate, norethisterone
-e.g.Microgynon/ Levest/ Rigevidon/ Ovranette/ Cilest/ Loestrin

headache, breast pain, depressed mood, weight gain, nausea, abdominal pain

-desogestrel with ethinylestradiol
-drospirenone with ethinylestradiol
-gestodene with ethinylestradiol

co-cyprindiol cyproterone acetate

•Stop 4 weeks before surgery and recommence at first menses at least 2 weeks after mobilisation
•If not possible to stop, use VTE prophylaxis (heparins/ compression hosiery)

progestogen only pills
•Alter cervical mucus to prevent sperm penetration
•Endometrial changes hinder implantation

•Those with CV risks (VTE or arterial thromboembolic risk)
-Women about to undergo major surgery, surgery on the legs
-Women who have just given birthreastfeeders

-Desogestrel = 12 hours
-Levonorgestrel 30mcg (Norgeston®) = 3 hours

2 days in FSRH guidelines but 7 days in PIL of desogestrel, levonorgestrel

-Condoms
-Caps and Diaphragms

Intrauterine devices: •Copper bearing IUDs or progestogen-releasing intrauterine systems (IUS) work by stopping fertilisation from occurring and/or preventing implantation

-Contraceptive patch (brand name: Evra)
-Vaginal ring
-Parenteral progestogen-only contraceptives: implants/injections

•Levonorgestrel (LNG): 72 hours of unprotected sex/contraception failure
•Ulipristal acetate (UPA): 120 hours of unprotected sex/contraception failure
•Cu-IUD: effective if inserted within 120 hours (5 days) of first unprotected sex/contraception failure in cycle or within 5 days of earliest estimated date of ovulation

Pregnancy prevention programmes
Used in situtations where the drug has potential for:
-a teratogenic effect (can cause birth defects),
-an adverse effect on the (neuro-) development of the child through exposure in-utero (in the womb

-Valproate
-Oral retinoids e.g. isotretinoin
-thalidomide

-Vomitting/emesis
-Pregnancy induced HT
-Convulsions (eclampsia)
-gestational diabetes
-infection

1.Influenza vaccine
2.Pertussis (whooping cough) vaccine
3.COVID-19 vaccines (booster for those already vaccinated)

Live attenuated vaccines:
•MMR vaccine
•BCG vaccine
•Chickenpox vaccine
•Oral typhoid vaccine (travel vaccine)
•Yellow fever vaccine (travel vaccine)

- Increase in progesterone, nausea & vomiting --> Decrease in absorption of oral medications
-Increase in tissue perfusion--> Increase in IM/SC absorption and transdermal absorption
-Increase in cardiac output, tidal vol & alveolar uptake--> Increase in absorption of drugs by inhalation

-Plasma volume increases by 150% (gestation) --> Vd increases --> clinical/therapeutic effect decreases

-Elevated hormonal concentrations of various hormones such as oestrogen, progesterone, prolactin and placental growth hormone --> Altered drug metabolism

-Increase in renal blood flow to the kidneys--> increase of glomerular filtration rate (GFR) by 50% in the first trimester and by 80% in the 2nd trimester--> increased elimination

-Mwt of drug - decreased transfer as size increases.
-Highly protein bound drugs tend to have higher maternal and lower fetal concentrations
-lipophilic, unionised drugs cross the placenta more easily than polar drugs
-pKa - weak bases can get 'trapped' in the fetal circulation because of the slightly lower pH (>H+ ions) compared with the maternal plasma.

'Any agent that results in structural or functional abnormalities in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy.'

38 weeks

1. Pre-embryonic
2. Embryonic
3. Fetal
(1st, 2nd, 3rd trimerster)

- Organogensis occurs mainly here
•Exposure to drug during this period = greatest risk of major birth defects
•Reason why women are advised to avoid/minimise drug use in 1st trimester

-LiCO3
-Tobacco/alcohol
-Methotrexate
-Retinoic acid
-Tetracyclines
-Phenytoin
-Thalidomide
-5‐alpha‐reductase inhibitors (finasteride and dutasteride)

ACEi a should be avoided in 2nd and 3rd trimester
NSAIDs should be avoided in the 3rd trimester

E1: weak form of estrogen and the only type found in women after the menopause
E2: most potent type of estrogen produced by the ovaries
E3: least potent of the estrogens and is a waste product made after the body uses estradiol

Management of:
-Menopausal symptoms
•Osteoporosis prophylaxis
•Improval of the vaginal epithelium

Ethinylestradiol: oral contraceptive in combo with progestins

Easy passage of drugs through breastmilk due to wide intercellular gaps in the milk ducts to allow passage of immunoglobins

alveolar cells swell under the influence of prolactin and subsequently close the intercellular gaps
-hence, drugs must pass across the cell membranes

-Infant plasma levels are most accurate indicator of drug exposure
-estimates infant drug exposure via breast milk

•Highly plasma protein bound (<90%)
•Low milk:plasma ration (<1)
•Low pKa
•Poor oral bioavailability
•Large molecular weight
•Half life < 24 hrs
•Low relevant infant dose (RID)

-paracetamol, oral/topical NSAIDs, bulk and osmotic laxatives, loperamide

-Codeine: metabolism varies between individuals; some may concentrate the drugs into milk
-Aspirin (high dose): associated with Reye's syndrome
-Meds that can cause drowsiness e.g. diphenhydramine --> can pass BBB--> sedation & can reduce milk supply
-Herbal remedies: lack of data

•Cytotoxic agents
•Amiodarone
•Lithium
•Isotretinoin

-Abx
-Antidepressants: Sertraline or citalopram (SSRIs) are the first-line drugs of choice

-Breastfeeding should be suspended/stopped as a last option
-The minimum clinically effective dose should be used for the shortest possible time
-Avoid new drugs if there is a therapeutic equivalent with data to support use in lactation

Pros:
•Relatively LSA
•Rich blood supply;
•Low metabolic activity;
•Relatively high permeability to many drugs;
•Ease of administration;
•Prolonged retention is possible;
•Offers the potential to achieve zero-order controlled release.

•Limited to potent molecules;
•Adverse effects (for example, local irritation)
•Hormone-dependent changes;
•Leakage;
•Life-cycle constraints;
•Applicability constraints

-GnRH: gonadotropin-releasing hormone
-FSH stimulates the ovaries
-LH stimulates ovulation and corpus luteum

Androgens, Oestrogens, Progesterone and inhibin

follicular phase, ovulatory phase, luteal phase

•P and E combined have a negative feedback effect on the pituitary and hypothalamus, inhibiting both LH and FSH secretion

Providing P is low, high level of E (as occurs at end of follicular phase) has positive feedback action on Hypothalamus & Pituitary --> ovulation

Proliferative Phase
Oestrogens (E):
•increase thickness of endometrium
•promote secretion of thin 'sperm-friendly' mucus

Secretory phase
Progestogen (P):
•endometrial swelling
•increases blood supply, lipid and glycogen deposition

Menstruation
•sudden decrease of E and P at end of luteal phase-->necrosis in the endometrium
•Aided by uterine prostaglandins

when follice development and ovulation ceases
-•Decreased production of ovarian hormones
-Raised FSH and LH

-Night sweats
-Mood swings
-Sleep disturbance
-Gas
-flushes

fluid retention, breast pain, vaginal bleeding, CV and breast, ovarian and cancer risk

-Women without a uterus: oestrogen only HRT, usually continuous
-Women with intact uterus: combined HRT (oestrogen and progestogen)

•Failure to conceive after having regular unprotected sex for more than 12 months (or less, if you're over 35)

Both LH and FSH gonadotrophins

Clompiphene citrate: patients where ovulatory dysfunction is shown e.g. PCOS
-Letrozole: breast cancer --> off-label

•Group I: hypothalamic pituitary failure (hypothalamic amenorrhoea)
•Group II: hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary syndrome (PCOS))
•Group III: ovarian failure

Regular, heavy & prolonged periods - due to increased uterine vasodilation and reduced haemostasis associated with increased PGE2, PGI2 and prostacyclin

Endometrialterine tissue growing outside the uterus

•Gonads:
Testes
•Reproductive tract:
Epididymis
Ductus (Vas) Deferens
Urethra
External genitalia
•External Genitalia:
Penis
Corpora cavernosa
Corpus spongiosum
•Accessory Glands:
Prostate
Seminal Vesicles
Bulbourethral Glands

sperm production and hormone production

Leydig: outside tubules
Sertoli: within tubules
Germ cells

LH--> leydig cells--> testosterone
FSH--> sertoli cells --> inhibin

-Promotes muscle growth responsible for male body conformation
- bone growth at puberty
-Induces male pattern of hair growth (i.e. beard)
-Causes deepening of voice
-Skin thickens & sebaceous glands thicken (acne)

-decreasing levels of testosterone
-Gamete (sperm) production continues
-low libido, fatigue and lack of energy, osteporosis

-Corpus cavernosum
-corpus spongiosum
-cavernous sinuses: blood vessels

increased ACh (parasympathetic) and decreased noradrenaline (sympathetic) release => increased eNOS (nitric oxide synthase) => increased NO--> dilation-->
Increase in blood flow into the corpus cavernosum and corpus spongiosum => erection

Ach & neuronal nNOS released from cavernous nerve--> makes eNOS in the vascular endothelial cells
-NO diffuses into surrounding vascular SMA & binds/activates guanylyl cylcase --> GTP --> cCGMP--> activates PKG--> smooth muscle relaxation
-Decrease in cytostolic calcium initiated by PKG --> vascular SM relaxation--> erection

-diabetes
-Smoking
-excessive alcohol
-Some drugs e.g. anti-hypertensives

competitively inhibits the enzyme responsible for the degradation of cGMP to GMP-->phosphodiesterase type 5 (PDE5).

-Persistent, painful erection lasting > 4 hours; in absence of sexual stimulation/desire
—ischemic (no-flow) - obstruction in venous drainage
-non-ischemic (high-flow) - excess arterial supply

-Alpha-adrenoreceptor blockers: relaxes muscle fibres within prostate e.g. tamsulosin
-5-alpha reductase inhibitors; inhibits prostate growth e.g. finasteride

Hormone therapy:
-Injections/implants to block production of androgen e.g. goserelin
-Anti-androgens to block androgen action e.g. bicalutamide