Week 7 - Contraception, Hormones & Osteoporosis

How long does the menstrual cycle last?

28 days (21-35 day range)

2 main phases of menstrual cycle?

follicular phase and luteal phase

What is the function GnRH?

stimulates release of FSH and LH from anterior pituitary (source: hypothalamus)

What is the function of FSH?

Stimulates follicle development and estrogen production (source: Anterior Pituitary)

What is the function of LH?

Triggers ovulation and corpus luteum formation (source: Anterior pituitary)

What is the function of estrogen?

promote the proliferation of the endometrium and modulates (FSH/LH), sourced by the ovarian follicles

What is the function of progesterone?

prepares uterus for pregnancy via endometrial stabilization and inhibition of LH/FSH; sourced by the corpus luteum

What is hCG?

human chorionic gonadotropin - maintains corpus luteum during pregnancy (source - trophoblast)

What occurs during the follicular phase?

- Menstruation (Days 1-5) - Shedding of the endometrial lining

- Follicular maturation - 1) hypothalamus secretes GnRH to stimulate anterior pituitary gland to release FSH and LH 2) Estrogen promotes endometrial proliferation

Primary Hormones associated with Follicular Phase

- Increase in FSH

- Increase in Estrogen

- Decrease in Progesterone

When is ovulation day? What happens?

Ovulation Day - Day 14

- LH surge causing rupture of dominant follicle and release of ovum; ruptured follicle becomes corpus luteum

What is the Luteal Phase?

- Occurs days 15-28

- If no fertilization - corpus luteum degenerates

- If fertilization - embryo secretes hcG to maintain corpus luteum

Hormones present in the luteal phase?

- Progesterone - stabilize endometrial lining

- Estrogen - supports endometrium

7 Types of hormonal contraception

1) Combined Oral Contraceptives (COCs) - Estrogen + Progestin

2) Progestin-only pills (POPs) - Progestin

3) Injectable (ex. IM - Depo-Provera) - Progestin

4) Implant (ex. subdermal - Nexplanon) - Progestin

5) Transdermal patch - Estrogen + Progestin

6) Vaginal Ring - Estrogen + Progestin

7) IUD (hormonal) - Mirena - Progestin only

What is the MOA of BC with Estrogen?

- Inhibits FSH release -> prevents follicular development

- Stabilizes endometrial lining -> reduces breakthrough bleeding

- Promote cycle control

What is the MOA of BC with Progestin?

- Inhibits LH surge -> prevents ovulation

- Thickens cervical mucus -> inhibits sperm penetration

- Thins endometrium -> inhibits implantation

What birth control forms undergo hepatic metabolism?

Oral forms

What birth control forms offer a longer duration of action?

- Injectables and implants

What type of interactions reduce the effectiveness of birth control?

Interactions with CYP450 inducers (ex. Rifampin, phenytoin)

What are the absolute contraindications for estrogen containing BC?

- Hx of VTE (DVT/PE)

- Migraines with Aura

- Smoker above 35 y.o.

- Current breast cancer pt

- Active liver disease

- Pregnancy

- Uncontrolled HTN

What are the absolute contraindications of progestin containing BC?

- Current breast cancer

- Active liver disease

- Pregnancy

- Undiagnosed vaginal bleeding

What progestin-only BC may cause risk of osteoporosis?

Depo-Provera

What are the Estrogen + Progestin (Combined Hormonal Contraceptives) Forms?

- Combined Oral Contraceptives

- Transdermal patch

- Vaginal Ring

What is the MOA for Combined Hormonal Contraceptives?

- Estrogen - Inhibits FSH -> prevents follicular development

- Progestin - Inhibits LH surge -> suppresses ovulation; thickens cervical mucus; thins endometrium

ADRs of combined hormonal contraceptives

- Increased VTE

- HTN

- Nausea/vomiting

- Breast tenderness

- Headaches

- Breakthrough bleeding

- Mood changes

- Hepatic Adenomas

What increases the risk for a thrombotic event when taking a combined hormonal contraceptive?

- Smoking

- Age 35 y.o. or older

- obesity

- immobility

What are the Progestin only contraceptives?

- Progestin-only pills (POPs)

- Injectables (Depo-Provera)

- Implants (Nexplanon)

- Hormonal IUDs (Mirena, Skyla)

What is the MOA of Progestin only contraceptives?

- Thickens cervical mucus

- Suppresses LH surge

- Thins endometrial lining

ADRs of progestin only contraceptives

- Irregular bleeding

- Amenorrhea

- Weight gain

- Mood change/depression

- Decreased libido

- Hirsutism

- Delayed return to fertility (w/ depo)

- Acne

What are the relative contraindications of BC?

- Hx of breast cancer >5 yrs

- Severe CV disease

- Severe Depression

- Osteoporosis risk

Drug interactions with COC

- CYP3A4 inducers (rifampin)

- CYP3A4 inhibitors (cimetidine, grapfruit juice)

- Antibiotics (broad-spectrum, penicillin's, bactrim)

Health Benefits of Combined Hormonal Contraception?

- Decreased Risk of:

- Dysmenorrhea

- menstrual blood loss and anemia

- PMS symptoms

- ectopic pregnancy

- Endometrial and ovarian cancer

- benign breast conditions

- PID

What is drospirenone?

A form of synthetic progestin used in Yaz-type contraceptives that has anti-androgenic and anti-mineralocorticoid effect

ADRs of dropirenone?

blocked Aldosterone effects

- Hyperkalemia

- Minimized salt and water retention

- Possible decrease in BP

- Increased risk of blood clots

What is the dosing for the vaginal ring?

Inserted for 3 weeks; removed for 1 week

What is the dosing for the transdermal patch?

Applied once per week for 3 weeks

What is the generic name of Progestin Only OCs?

Norethethidrone 0.35 mg

What is the dosing schedule for Progestin only injections (e.g. DepoProvera)?

Given every 3 months

What birth control method can cause infertility up to a year?

DepoProvera (Progestin only injections)

What birth control method has an increased risk for bone density loss?

DepoProvera

A breastfeeding mother presents to your clinic to discuss birth control options. Which options are preferred for her?

Progestin-Only (POPs, IUD, implant

A woman with a hx of VTE and migraine with aura presents to your clinic to discuss birth control options. Which options are preferred for her?

Progestin Only

A woman who wants regular monthly periods presents to your clinic to discuss birth control options. Which options are preferred for her?

Combined Hormonal

A woman who desired long-term/low maintenance birth control wants to discuss her options. What options are preferred for her?

LARC (implant or IUD)

A woman who needs contraception but also desires acne controls comes to you for recommendations. What options are preferred for her?

Combined (w/ anti-androgenic progestin)

What are emergency contraceptive methods?

- Copper IUD

- Ulipristal acetate (Ella)

- Levonorgestrel (Plan B)

- Yuzpe regimen

What emergency contraceptive method is less effective in pts with higher BMI?

Plan B

What is the MOA of emergency contraception?

- Delays or inhibits ovulation (Ulipristal, LNG)

- Alters sperm function or movement (LNG, Copper IUD)

- Prevents fertilization or implantation (Copper IUD)

- Alters endometrial receptivity (Uliprisital, IUD)

Side effects associated with LNG or Ulipristal

- Nausea

- Fatigue

- Headache

- Delayed/early menses

Side effects associated with Yuzpe

Nausea and vomiting

Side effects associated with Copper IUD

- Cramping w/ insertion

- Heavier menses

- Dysmenorrhea

Drug interactions w/ Ulipristal

Hormonal contraceptives - may reduce efficacy so avoid for 1st 5 days

Drug interactions w/ LNG

CYP3A4 Inducers (rifampin, phenytoin)

Drug interactions w/ IUD

None

What pills are used for medical abortion?

- Mifepristone

- Misoprostel

What are ADRs of Mifepristone and Misoprostel?

- Bleeding

- Cramping

- GI effects

How is menopause diagnosed?

amenorrhea for 12 months

What hormonal changes are associated with menopause?

- Decreased estrogen, progesterone and androgens

- Increased FSH & LH

Clinical Manifestations of menopause

- Vasomotor symptoms (hot flashes, night sweats)

- Genitourinary Syndrome on Menopause (GSM) - vaginal dryness, irritation, dyspareunia, urinary urgency recurrent UTIs

- Mood changes

- sleep disturbance

- decreased libido

- joint aches

- brain fog

Long term risk of menopause due to estrogen deficiency include....

- Osteoporosis

- CV Disease

- Cognitive decline

- GU atrophy

Management for Menopause's vasomotor symptoms

- 1st line - Hormone Therapy - Estrogen + Progestin for women w/ a uterus and Estrogen only for women w/o a uterus

- Non-hormonal options (SSRIs/SNRIs, gabapentin, clonidine, fezolinetant)

MOA of SSRIs/SNRIs

Modulate serotonin and norepi levels in the thermoregulatory center of the hypothalamus

MOA of Gabapentin

Involves central thermoregulation control via calcium channels and GABA modulation

Management of Menopause's GU symptoms

- Vaginal Estrogen (creams, rings and tablets)

- Non-hormonal options (OTC lubricants and moisturizers)

What is osteoporosis?

A condition that causes more bone resorption than bone formation, resulting in a net loss of bone

What is the function of osteoclasts vs osteoblasts?

Osteoclasts - Bone resorption (crush bone)

Osteoblasts - Bone formation (build bone)

Non-modifiable risk factors of Osteoporosis

- Age > 65

- Females

- Postmenopausal women

- Caucasian/Asian Ethnicity

- Family Hx

Modifiable risk factors for osteoporosis

- Low calcium/vitamin D intake

- Smoking

- Alcohol (>3 drinks/day)

- Inactivity

- Low BMI/body weight

Treatment for Osteoporosis - Lifestyle modifications

- Weight-bearing and resistance exercises

- Fall prevention

- Smoking cessation & moderate alcohol intake

- Adequate calcium and vitamin D intake

What are the two types of pharmacotherapy agents for Osteoporosis

1) Anti-resorptive agents - inhibit bone breakdown

2) Anabolic Agents - Stimulate new bone formation

What are the 5 anti-resorptive agents to help tx osteoporosis?

- Bisphosphonates

- Denosumab

- Selective Estrogen Receptor Modulators (SERMs)

- Hormone Replacement Therapy (HRT)

- Calcitonin

What are the Anabolic Agents used to tx osteoporosis?

- Teriparatide

- Abaloparatide

- Romosozumab

MOA of bisphosphonates

Inhibit farnesyl pyrophosphate synthase in osteoclast, inducing osteoclast apoptosis

ADRs of bisphosphonates

- Esophagittis, GI upset

- Osteonecrosis of the jaw

- Atypical femur facture

Bisphophonate Drugs

- Alendronate

- Risedronate

- Ibandronate

- Zoledronic Acid

MOA of Denosumab

Monoclonal Ab against RANKL, blocking osteoclast formation

ADR of Denosumab

- Rebound fractures

- Hypocalcemia

Drugs w/i the SERM class

Raloxifene

ADRs of SERMs

- Hot flashes

- VTE

- Non-effective for non-vertebral or hip fractures

What risk factors should be considered when deciding to use HRT therapy?

Use w/ caution if pt has:

- breast cancer

- VTE

- Stroke

- CAD

MOA of calitonin

Direct inhibition of osteoclast activity

MOA of teriparatide

Pulsatile PTH stimulates osteoblasts more than osteoclasts

ADRs of Teriparatide

- Hypercalcemia

- Osteosarcoma

Abaloparatide (Tymlos)

parathyroid hormone analog

MOA of romosozumab (Evenity)

Monoclonal antibody that inhibits sclerostin, a glycoprotein that inhibits bone formation

Increased bone formation and decreased bone reabsorptio

ADRs of romosozumab

- CV events

- Hypocalcemia

1st line pharmacological tx for osteoporosis

Bisphosphonates